{"entity": "journal", "iuid": "24326cfa9af74978b3169a5126a9020e", "timestamp": "2026-06-11T22:35:54.973Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Cancers%20%28Basel%29.json"}, "display": {"href": "https://publications.scilifelab.se/journal/Cancers%20%28Basel%29"}}, "title": "Cancers (Basel)", "issn": "2072-6694", "issn-l": "2072-6694", "publications_count": 32, "publications": [{"entity": "publication", "iuid": "57ccb7a2e57747c5885ff80d4f036529", "links": {"self": {"href": "https://publications.scilifelab.se/publication/57ccb7a2e57747c5885ff80d4f036529.json"}, "display": {"href": "https://publications.scilifelab.se/publication/57ccb7a2e57747c5885ff80d4f036529"}}, "title": "Single-Cell Comparison of Small Intestinal Neuroendocrine Tumors and Enterochromaffin Cells from Two Patients.", "authors": [{"family": "Axling", "given": "Fredrik", "initials": "F", "orcid": "0000-0003-3748-3176", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d84ca11d6f2449583a0fa81eaf1e64c.json"}}, {"family": "Barazeghi", "given": "Elham", "initials": "E"}, {"family": "Hellman", "given": "Per", "initials": "P", "orcid": "0000-0002-5322-5073", "researcher": {"href": "https://publications.scilifelab.se/researcher/7c7a23c0741d444b82657b10fc7a4916.json"}}, {"family": "Norl\u00e9n", "given": "Olov", "initials": "O"}, {"family": "Backman", "given": "Samuel", "initials": "S"}, {"family": "St\u00e5lberg", "given": "Peter", "initials": "P", "orcid": "0000-0002-9625-1394", "researcher": {"href": "https://publications.scilifelab.se/researcher/6698ec6bc9a44d9d84edd62232083ec1.json"}}], "type": "journal article", "published": "2026-01-29", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "18", "issue": "3", "issn-l": "2072-6694"}, "abstract": "Several studies have attempted to identify the initiating drivers of small intestinal neuroendocrine tumor (SI-NET) development and the molecular mechanisms underlying their progression and metastatic spread. Previous gene expression studies have used bulk microarrays or RNA sequencing to compare tumor tissue with normal intestinal mucosa. However, the intestine comprises multiple distinct cell types, and bulk analyses are limited by this cellular heterogeneity, which can confound tumor-specific signals.\n\nWe performed single-cell RNA sequencing on primary SI-NETs and paired normal mucosa from two patients to directly compare tumor cells with their cells of origin, the enterochromaffin (EC) cells. To minimize type I errors, we applied a two-step validation strategy by overlapping differentially expressed genes with an external single-cell dataset and cross-referencing candidate genes for enteroendocrine expression in the Human Protein Atlas.\n\nFor further distinction and characterization, ECs were subdivided into serotonergic and non-serotonergic clusters. This analysis revealed that the SI-NET cells are transcriptionally more similar to serotonergic ECs, consistent with serum metabolite profiles derived from clinical parameters. Our analyses uncovered a loss-of-expression program characterized by regulators of epithelial differentiation and in parallel, a gain-of-expression program displayed neuronal signaling gene induction, implicating functional reprogramming toward neuronal-like properties. Together, these specific losses and gains suggest that our patient-derived SI-NETs undergo adaptation through both loss of enteroendocrine functions and acquisition of neurobiological-promoting signaling pathways.\n\nThese findings nominate candidate drivers for further functional validation and highlight potential therapeutic strategies in our patient cohort, including restoring suppressed Notch signaling and targeting aberrant neuronal signaling networks. However, even with a two-step validation procedure, the modest cohort size limits statistical power and generalizability, particularly for the proposed association to a serotonergic phenotype. Larger, multi-patient single-cell studies are required to confirm these mechanisms and establish their clinical relevance.", "doi": "10.3390/cancers18030435", "pmid": "41681906", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "NGI Short read": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12897003"}, {"db": "pii", "key": "cancers18030435"}], "notes": [], "created": "2026-06-01T08:42:46.361Z", "modified": "2026-06-01T08:42:47.207Z"}, {"entity": "publication", "iuid": "9e68a455ebfb445fb36a31627cb0b31b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9e68a455ebfb445fb36a31627cb0b31b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9e68a455ebfb445fb36a31627cb0b31b"}}, "title": "Prospective Screening of Cancer Syndromes in Patients with Mesenchymal Tumors.", "authors": [{"family": "\u00d6fverholm", "given": "Ingegerd", "initials": "I", "orcid": "0000-0002-6907-8004", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ba94eeea4d24e9c8c354fe1256fd0ce.json"}}, {"family": "Lin", "given": "Yingbo", "initials": "Y", "orcid": "0000-0001-7190-2261", "researcher": {"href": "https://publications.scilifelab.se/researcher/3dfabc46c47741b9ace94b082d60184d.json"}}, {"family": "Mondini", "given": "Julia", "initials": "J"}, {"family": "Hardingz", "given": "John", "initials": "J"}, {"family": "Br\u00e4nstr\u00f6m", "given": "Robert", "initials": "R", "orcid": "0000-0001-6245-7223", "researcher": {"href": "https://publications.scilifelab.se/researcher/3a5818dd9c4e4b9eae136c135d411c66.json"}}, {"family": "Tsagkozis", "given": "Panagiotis", "initials": "P", "orcid": "0000-0002-6631-2053", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae792176785f4fb3b5a1eb36478570f7.json"}}, {"family": "Wirta", "given": "Valtteri", "initials": "V", "orcid": "0000-0003-3811-5439", "researcher": {"href": "https://publications.scilifelab.se/researcher/cba024b2e3c347f6b981922d984ad2d6.json"}}, {"family": "Gellerbring", "given": "Anna", "initials": "A"}, {"family": "Lindberg", "given": "Johan", "initials": "J"}, {"family": "Chellappa", "given": "Venkatesh", "initials": "V"}, {"family": "Mayrhofer", "given": "Markus", "initials": "M"}, {"family": "Haglund", "given": "Cecilia", "initials": "C"}, {"family": "Haglund de Flon", "given": "Felix", "initials": "F"}, {"family": "Wallander", "given": "Karin", "initials": "K", "orcid": "0000-0001-8166-9678", "researcher": {"href": "https://publications.scilifelab.se/researcher/db174787efd74dc1b84f1bf56b74a22d.json"}}], "type": "journal article", "published": "2024-11-13", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "16", "issue": "22", "pages": "3816", "issn-l": "2072-6694"}, "abstract": "The etiology of most mesenchymal tumors is unknown, and knowledge about syndromes with an increased risk of tumors in bone or soft tissue is sparse.\n\nWe present a prospective germline analysis of 312 patients with tumors suspected of being sarcomas at a tertiary sarcoma center. Germline and tumor whole genome sequencing, tumor transcriptome, and methylome analyses were performed.\n\nGermline pathogenic or likely pathogenic variants associated with an increased risk of tumors were detected in 24 patients (8%), of which 11 (4%) harbored a detectable second hit in the tumor. Second hits were confirmed in genes with (NF1, RB1, TP53, EXT2, and SDHC) and without (ATM, CDC73, MLH1, MSH6, POLG, and KCNQ1) known association with mesenchymal tumor predisposition. Sarcomas from two Lynch syndrome patients showed mismatch repair deficiency, predicting a treatment response to immune checkpoint inhibitors (Level 1 biomarker according to the FDA (Federal Drug Administration) and ESMO (European Society for Medical Oncology)). None of the three CHEK2 carriers had a second hit in the tumor, suggesting a weak link to sarcoma.\n\nWe conclude that second-hit analyses can be used in standard of care to identify syndrome-related tumors. This approach can help distinguish true manifestations of tumor syndromes from unrelated germline findings and enhance the understanding of germline predisposition in soft tissue tumors. Prospective screening using germline whole genome sequencing should be considered when comprehensive somatic sequencing is introduced into clinical practice.", "doi": "10.3390/cancers16223816", "pmid": "39594770", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Clinical Genomics Stockholm": "Service", "Bioinformatics (NBIS)": "Collaborative", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11592761"}, {"db": "pii", "key": "cancers16223816"}], "notes": [], "created": "2024-11-14T08:02:41.749Z", "modified": "2025-11-18T20:44:32.464Z"}, {"entity": "publication", "iuid": "6fcc035591104439ae67749286e15ac2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6fcc035591104439ae67749286e15ac2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6fcc035591104439ae67749286e15ac2"}}, "title": "CRISPR-Cas9 Knockout Screens Identify DNA Damage Response Pathways and BTK as Essential for Cisplatin Response in Diffuse Large B-Cell Lymphoma.", "authors": [{"family": "Issa", "given": "Issa Ismail", "initials": "II"}, {"family": "Due", "given": "Hanne", "initials": "H"}, {"family": "Br\u00f8ndum", "given": "Rasmus Froberg", "initials": "RF", "orcid": "0000-0001-5537-6767", "researcher": {"href": "https://publications.scilifelab.se/researcher/8b478b3c355742d7a0f7e05bc830dfa6.json"}}, {"family": "Veeravakaran", "given": "Vidthdyan", "initials": "V", "orcid": "0009-0008-4046-3612", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7902e96a2d1495dba45da681a9aedb5.json"}}, {"family": "Haraldsd\u00f3ttir", "given": "Hulda", "initials": "H"}, {"family": "Sylvester", "given": "Cathrine", "initials": "C", "orcid": "0009-0002-5277-9434", "researcher": {"href": "https://publications.scilifelab.se/researcher/57cc8c271e1945debc4dc9269f989452.json"}}, {"family": "Brogaard", "given": "Asta", "initials": "A"}, {"family": "Dhanjal", "given": "Soniya", "initials": "S"}, {"family": "Schmierer", "given": "Bernhard", "initials": "B", "orcid": "0000-0002-9082-7022", "researcher": {"href": "https://publications.scilifelab.se/researcher/d3ee96f9eb454850be6db3318b28479f.json"}}, {"family": "Dybk\u00e6r", "given": "Karen", "initials": "K", "orcid": "0000-0003-2488-435X", "researcher": {"href": "https://publications.scilifelab.se/researcher/d3fd29e2afa6431fac9f504ab22b3c56.json"}}], "type": "journal article", "published": "2024-07-02", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "issn-l": "2072-6694", "volume": "16", "issue": "13", "pages": "2437"}, "abstract": "The recurrence of diffuse large B-cell lymphoma (DLBCL) has been observed in 40% of cases. The standard of care for refractory/relapsed DLBCL (RR-DLBCL) is platinum-based treatment prior to autologous stem cell transplantation; however, the prognosis for RR-DLBCL patients remains poor. Thus, to identify genes affecting the cisplatin response in DLBCL, cisplatin-based whole-genome CRISPR-Cas9 knockout screens were performed in this study. We discovered DNA damage response (DDR) pathways as enriched among identified sensitizing CRISPR-mediated gene knockouts. In line, the knockout of the nucleotide excision repair genes XPA and ERCC6 sensitized DLBCL cells to platinum drugs irrespective of proliferation rate, thus documenting DDR as essential for cisplatin sensitivity in DLBCL. Functional analysis revealed that the loss of XPA and ERCC6 increased DNA damage levels and altered cell cycle distribution. Interestingly, we also identified BTK, which is involved in B-cell receptor signaling, to affect cisplatin response. The knockout of BTK increased cisplatin sensitivity in DLBCL cells, and combinatory drug screens revealed a synergistic effect of the BTK inhibitor, ibrutinib, with platinum drugs at low concentrations. Applying local and external DLBCL cohorts, we addressed the clinical relevance of the genes identified in the CRISPR screens. BTK was among the most frequently mutated genes with a frequency of 3-5%, and XPA and ERCC6 were also mutated, albeit at lower frequencies. Furthermore, 27-54% of diagnostic DLBCL samples had mutations in pathways that can sensitize cells to cisplatin. In conclusion, this study shows that XPA and ERCC6, in addition to BTK, are essential for the response to platinum-based drugs in DLBCL.", "doi": "10.3390/cancers16132437", "pmid": "39001501", "labels": {"CRISPR Functional Genomics": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11240649"}, {"db": "pii", "key": "cancers16132437"}], "notes": [], "created": "2024-07-04T10:15:48.777Z", "modified": "2026-03-18T09:39:51.639Z"}, {"entity": "publication", "iuid": "194b877bbe6b45eaaafbb8b0c4fb83df", "links": {"self": {"href": "https://publications.scilifelab.se/publication/194b877bbe6b45eaaafbb8b0c4fb83df.json"}, "display": {"href": "https://publications.scilifelab.se/publication/194b877bbe6b45eaaafbb8b0c4fb83df"}}, "title": "Quantification and Profiling of Early and Late Differentiation Stage T Cells in Mantle Cell Lymphoma Reveals Immunotherapeutic Targets in Subsets of Patients.", "authors": [{"family": "Lokhande", "given": "Lavanya", "initials": "L"}, {"family": "Nilsson", "given": "Daniel", "initials": "D", "orcid": "0009-0001-6214-198X", "researcher": {"href": "https://publications.scilifelab.se/researcher/23bd6c87f0f147219e68f7a52d71e6dc.json"}}, {"family": "de Matos Rodrigues", "given": "Joana", "initials": "J"}, {"family": "Hassan", "given": "May", "initials": "M"}, {"family": "Olsson", "given": "Lina M", "initials": "LM", "orcid": "0000-0002-1359-0295", "researcher": {"href": "https://publications.scilifelab.se/researcher/195cc23b0d3a48dd8d27995fbd7469ac.json"}}, {"family": "Pyl", "given": "Paul-Theodor", "initials": "PT", "orcid": "0000-0002-7651-883X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a69051a0275c442c8c0d5621b4000929.json"}}, {"family": "Vasquez", "given": "Louella", "initials": "L"}, {"family": "Porwit", "given": "Anna", "initials": "A"}, {"family": "Gerdtsson", "given": "Anna Sandstr\u00f6m", "initials": "AS", "orcid": "0000-0003-1932-0365", "researcher": {"href": "https://publications.scilifelab.se/researcher/d2092b7829e2419f97169f5201219c47.json"}}, {"family": "Jerkeman", "given": "Mats", "initials": "M"}, {"family": "Ek", "given": "Sara", "initials": "S", "orcid": "0000-0002-1388-4912", "researcher": {"href": "https://publications.scilifelab.se/researcher/56861b5f5cac4b23ab86b19b4650aa3d.json"}}], "type": "journal article", "published": "2024-06-21", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "16", "issue": "13", "issn-l": "2072-6694"}, "abstract": "With the aim to advance the understanding of immune regulation in MCL and to identify targetable T-cell subsets, we set out to combine image analysis and spatial omic technology focused on both early and late differentiation stages of T cells. MCL patient tissue (n = 102) was explored using image analysis and GeoMx spatial omics profiling of 69 proteins and 1812 mRNAs. Tumor cells, T helper (TH) cells and cytotoxic (TC) cells of early (CD57-) and late (CD57+) differentiation stage were analyzed. An image analysis workflow was developed based on fine-tuned Cellpose models for cell segmentation and classification. TC and CD57+ subsets of T cells were enriched in tumor-rich compared to tumor-sparse regions. Tumor-sparse regions had a higher expression of several key immune suppressive proteins, tentatively controlling T-cell expansion in regions close to the tumor. We revealed that T cells in late differentiation stages (CD57+) are enriched among MCL infiltrating T cells and are predictive of an increased expression of immune suppressive markers. CD47, IDO1 and CTLA-4 were identified as potential targets for patients with T-cell-rich MCL TIME, while GITR might be a feasible target for MCL patients with sparse T-cell infiltration. In subgroups of patients with a high degree of CD57+ TC-cell infiltration, several immune checkpoint inhibitors, including TIGIT, PD-L1 and LAG3 were increased, emphasizing the immune-suppressive features of this highly differentiated T-cell subset not previously described in MCL.", "doi": "10.3390/cancers16132289", "pmid": "39001353", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC11240320"}, {"db": "pii", "key": "cancers16132289"}], "notes": [], "created": "2024-11-12T12:12:24.656Z", "modified": "2024-11-12T12:25:49.750Z"}, {"entity": "publication", "iuid": "d7727b44644f4a45bf2e7b3843b07b3d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d7727b44644f4a45bf2e7b3843b07b3d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d7727b44644f4a45bf2e7b3843b07b3d"}}, "title": "Tumor Predisposing Post-Zygotic Chromosomal Alterations in Bladder Cancer-Insights from Histologically Normal Urothelium.", "authors": [{"family": "Sta\u0144kowska", "given": "Wiktoria", "initials": "W"}, {"family": "Sarkisyan", "given": "Daniil", "initials": "D"}, {"family": "Bruhn-Olszewska", "given": "Bo\u017cena", "initials": "B"}, {"family": "Duzowska", "given": "Katarzyna", "initials": "K"}, {"family": "Bie\u0144kowski", "given": "Micha\u0142", "initials": "M", "orcid": "0000-0002-9291-3928", "researcher": {"href": "https://publications.scilifelab.se/researcher/8227f94ec50e481fa45e9bec035b6708.json"}}, {"family": "J\u0105kalski", "given": "Marcin", "initials": "M", "orcid": "0000-0002-5481-9148", "researcher": {"href": "https://publications.scilifelab.se/researcher/e4411ec776b94c89b0444bd8d49672ca.json"}}, {"family": "W\u00f3jcik-Zalewska", "given": "Magdalena", "initials": "M"}, {"family": "Davies", "given": "Hanna", "initials": "H"}, {"family": "Dr\u0119\u017cek-Chy\u0142a", "given": "Kinga", "initials": "K", "orcid": "0009-0007-1008-7145", "researcher": {"href": "https://publications.scilifelab.se/researcher/5dbc662c14754a468de99e24a60cedf2.json"}}, {"family": "P\u0119ksa", "given": "Rafa\u0142", "initials": "R", "orcid": "0000-0002-4904-7059", "researcher": {"href": "https://publications.scilifelab.se/researcher/3dd33f6e4a9a49d6af2265bc91b77d4e.json"}}, {"family": "Harazin-Lechowska", "given": "Agnieszka", "initials": "A"}, {"family": "Ambicka", "given": "Aleksandra", "initials": "A"}, {"family": "Przewo\u017anik", "given": "Marcin", "initials": "M"}, {"family": "Adamczyk", "given": "Agnieszka", "initials": "A"}, {"family": "Sasim", "given": "Karol", "initials": "K"}, {"family": "Makarewicz", "given": "Wojciech", "initials": "W"}, {"family": "Matuszewski", "given": "Marcin", "initials": "M"}, {"family": "Biernat", "given": "Wojciech", "initials": "W"}, {"family": "J\u00e4rhult", "given": "Josef D", "initials": "JD", "orcid": "0000-0002-7075-1059", "researcher": {"href": "https://publications.scilifelab.se/researcher/2598129f86ee47ebafc696148f9da01f.json"}}, {"family": "Lipcsey", "given": "Mikl\u00f3s", "initials": "M", "orcid": "0000-0002-1976-4129", "researcher": {"href": "https://publications.scilifelab.se/researcher/81805f2324634628abefcf0ab6ce6a15.json"}}, {"family": "Hultstr\u00f6m", "given": "Michael", "initials": "M", "orcid": "0000-0003-4675-1099", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9a74d3380a24c31930e6e671e685b5b.json"}}, {"family": "Frithiof", "given": "Robert", "initials": "R", "orcid": "0000-0003-2278-7951", "researcher": {"href": "https://publications.scilifelab.se/researcher/8fec11dd18f941b7842610ad14237a35.json"}}, {"family": "Jaszczy\u0144ski", "given": "Janusz", "initials": "J"}, {"family": "Ry\u015b", "given": "Janusz", "initials": "J"}, {"family": "Genovese", "given": "Giulio", "initials": "G"}, {"family": "Piotrowski", "given": "Arkadiusz", "initials": "A"}, {"family": "Filipowicz", "given": "Natalia", "initials": "N", "orcid": "0000-0002-9673-2649", "researcher": {"href": "https://publications.scilifelab.se/researcher/153a4d73f8cb4ec68cedfd85556e383e.json"}}, {"family": "Dumanski", "given": "Jan P", "initials": "JP"}], "type": "journal article", "published": "2024-02-27", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "16", "issue": "5", "issn-l": "2072-6694"}, "abstract": "Bladder urothelial carcinoma (BLCA) is the 10th most common cancer with a low survival rate and strong male bias. We studied the field cancerization in BLCA using multi-sample- and multi-tissue-per-patient protocol for sensitive detection of autosomal post-zygotic chromosomal alterations and loss of chromosome Y (LOY). We analysed 277 samples of histologically normal urothelium, 145 tumors and 63 blood samples from 52 males and 15 females, using the in-house adapted Mosaic Chromosomal Alterations (MoChA) pipeline. This approach allows identification of the early aberrations in urothelium from BLCA patients. Overall, 45% of patients exhibited at least one alteration in at least one normal urothelium sample. Recurrence analysis resulted in 16 hotspots composed of either gains and copy number neutral loss of heterozygosity (CN-LOH) or deletions and CN-LOH, encompassing well-known and new BLCA cancer driver genes. Conservative assessment of LOY showed 29%, 27% and 18% of LOY-cells in tumors, blood and normal urothelium, respectively. We provide a proof of principle that our approach can characterize the earliest alterations preconditioning normal urothelium to BLCA development. Frequent LOY in blood and urothelium-derived tissues suggest its involvement in BLCA.", "doi": "10.3390/cancers16050961", "pmid": "38473323", "labels": {"NGI SNP genotyping": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10930680"}, {"db": "pii", "key": "cancers16050961"}], "notes": [], "created": "2024-03-21T08:55:56.265Z", "modified": "2024-03-21T08:55:57.016Z"}, {"entity": "publication", "iuid": "4036ea5cd46541d3aa846db00de8ef08", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4036ea5cd46541d3aa846db00de8ef08.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4036ea5cd46541d3aa846db00de8ef08"}}, "title": "Fluorometric Quantification of Total Cell-Free DNA as a Prognostic Biomarker in Non-Small-Cell Lung Cancer Patients Treated with Immune Checkpoint Blockade.", "authors": [{"family": "Oliver", "given": "Javier", "initials": "J", "orcid": "0000-0002-8073-4711", "researcher": {"href": "https://publications.scilifelab.se/researcher/097176806fcd49a996f7e153d99f5640.json"}}, {"family": "Onieva", "given": "Juan Luis", "initials": "JL", "orcid": "0000-0001-8976-8099", "researcher": {"href": "https://publications.scilifelab.se/researcher/64f312743c45466297c164d9074855cc.json"}}, {"family": "Garrido-Barros", "given": "Mar\u00eda", "initials": "M"}, {"family": "Cobo-Dols", "given": "Manuel", "initials": "M", "orcid": "0000-0003-3402-1144", "researcher": {"href": "https://publications.scilifelab.se/researcher/1073676fec6f45e09cf82b9496b123bd.json"}}, {"family": "Mart\u00ednez-G\u00e1lvez", "given": "Beatriz", "initials": "B"}, {"family": "Garc\u00eda-Pel\u00edcano", "given": "Ana Isabel", "initials": "AI"}, {"family": "Dubbelman", "given": "Jaime", "initials": "J"}, {"family": "Ben\u00edtez", "given": "Jos\u00e9 Carlos", "initials": "JC", "orcid": "0000-0002-8776-9132", "researcher": {"href": "https://publications.scilifelab.se/researcher/b306b1d50c0b4c4390c1ad28eba47120.json"}}, {"family": "Mart\u00edn", "given": "Juan Zafra", "initials": "JZ", "orcid": "0000-0003-4778-4271", "researcher": {"href": "https://publications.scilifelab.se/researcher/4c7177932eed44bda5145cc1d5ea3245.json"}}, {"family": "Cantero", "given": "Alejandra", "initials": "A"}, {"family": "P\u00e9rez-Ruiz", "given": "Elisabeth", "initials": "E", "orcid": "0000-0001-7204-0800", "researcher": {"href": "https://publications.scilifelab.se/researcher/ea96e2b1045d4b338bf7e4055630af74.json"}}, {"family": "Rueda-Dom\u00ednguez", "given": "Antonio", "initials": "A", "orcid": "0000-0001-5890-0149", "researcher": {"href": "https://publications.scilifelab.se/researcher/6fe1b9aa037c4ded9bcf9d1f10337899.json"}}, {"family": "Barrag\u00e1n", "given": "Isabel", "initials": "I", "orcid": "0000-0002-8586-6502", "researcher": {"href": "https://publications.scilifelab.se/researcher/b21619a3feff43a2bc28b5834c825d0c.json"}}], "type": "journal article", "published": "2023-06-26", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "15", "issue": "13", "issn-l": "2072-6694"}, "abstract": "The present study aimed to investigate the potential of basal cell-free fluorometric DNA (cfDNA) quantification as a prognostic biomarker in advanced non-small cell lung cancer (NSCLC) patients treated with an Immune Checkpoint Blockade (ICB). A discovery and validation cohort of 61 and 31 advanced lung cancer patients treated with ICB were included in this study. Quantification of cfDNA concentration was performed before the start of the treatment and patients were followed up for a median of 34 (30-40) months. The prognostic predicted value of cfDNA was evaluated based on ROC, and Cox regression was conducted via univariate and multivariate analyses to estimate the hazard ratio. We observed that a cfDNA cut-off of 0.55 ng/\u00b5L before the ICB determines the overall survival of patients with a log rank p-value of 3.3 \u00d7 10-4. That represents median survivals of 3.8 vs. 17.5 months. Similar results were obtained in the validation cohort being the log rank p-value 3.8 \u00d7 10-2 with median survivals of 5.9 vs. 24.3. The univariate and multivariate analysis revealed that the cut-off of 0.55 ng/\u00b5L before ICB treatment was an independent predictive factor and was significantly associated with a better survival outcome. High cfDNA concentrations identify patients with advanced NSCLC who do not benefit from the ICB. The determination of cfDNA is a simple test that could select a group of patients in whom new therapeutic strategies are needed.", "doi": "10.3390/cancers15133357", "pmid": "37444467", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10341133"}, {"db": "pii", "key": "cancers15133357"}], "notes": [], "created": "2023-11-27T22:02:11.176Z", "modified": "2024-01-16T13:48:33.106Z"}, {"entity": "publication", "iuid": "14f4d2b869aa4a2dabad06efa432aa96", "links": {"self": {"href": "https://publications.scilifelab.se/publication/14f4d2b869aa4a2dabad06efa432aa96.json"}, "display": {"href": "https://publications.scilifelab.se/publication/14f4d2b869aa4a2dabad06efa432aa96"}}, "title": "Simultaneous Ultra-Sensitive Detection of Structural and Single Nucleotide Variants Using Multiplex Droplet Digital PCR in Liquid Biopsies from Children with Medulloblastoma.", "authors": [{"family": "Arthur", "given": "Cecilia", "initials": "C", "orcid": "0000-0002-0645-6530", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b07104d934d413a9c9546e7e9933051.json"}}, {"family": "Jylh\u00e4", "given": "Cecilia", "initials": "C"}, {"family": "de St\u00e5hl", "given": "Teresita D\u00edaz", "initials": "TD", "orcid": "0000-0001-5933-6623", "researcher": {"href": "https://publications.scilifelab.se/researcher/2f51158ce6e14f3b96bf16a214689d1d.json"}}, {"family": "Shamikh", "given": "Alia", "initials": "A"}, {"family": "Sandgren", "given": "Johanna", "initials": "J"}, {"family": "Rosenquist", "given": "Richard", "initials": "R"}, {"family": "Nordenskj\u00f6ld", "given": "Magnus", "initials": "M"}, {"family": "Harila", "given": "Arja", "initials": "A"}, {"family": "Barbany", "given": "Gisela", "initials": "G", "orcid": "0000-0003-3185-2962", "researcher": {"href": "https://publications.scilifelab.se/researcher/13fda0d702d543f981898ebd53849817.json"}}, {"family": "Sandvik", "given": "Ulrika", "initials": "U", "orcid": "0000-0002-9273-2158", "researcher": {"href": "https://publications.scilifelab.se/researcher/72b8c0bf76054dc8ba15fa80fa78918e.json"}}, {"family": "Tham", "given": "Emma", "initials": "E", "orcid": "0000-0001-6079-164X", "researcher": {"href": "https://publications.scilifelab.se/researcher/6689dd9aff584082a57398141a538111.json"}}], "type": "journal article", "published": "2023-03-25", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "15", "issue": "7", "issn-l": "2072-6694"}, "abstract": "Medulloblastoma is a malignant embryonal tumor of the central nervous system (CNS) that mainly affects infants and children. Prognosis is highly variable, and molecular biomarkers for measurable residual disease (MRD) detection are lacking. Analysis of cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) using broad genomic approaches, such as low-coverage whole-genome sequencing, has shown promising prognostic value. However, more sensitive methods are needed for MRD analysis. Here, we show the technical feasibility of capturing medulloblastoma-associated structural variants and point mutations simultaneously in cfDNA using multiplexed droplet digital PCR (ddPCR). Assay sensitivity was assessed with a dilution series of tumor in normal genomic DNA, and the limit of detection was below 100 pg of input DNA for all assays. False positive rates were zero for structural variant assays. Liquid biopsies (CSF and plasma, n = 47) were analyzed from 12 children with medulloblastoma, all with negative CSF cytology. MRD was detected in 75% (9/12) of patients overall. In CSF samples taken before or within 21 days of surgery, MRD was detected in 88% (7/8) of patients with localized disease and in one patient with the metastasized disease. Our results suggest that this approach could expand the utility of ddPCR and complement broader analyses of cfDNA for MRD detection.", "doi": "10.3390/cancers15071972", "pmid": "37046633", "labels": {"NGI SNP genotyping": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10092983"}, {"db": "pii", "key": "cancers15071972"}], "notes": [], "created": "2023-11-29T11:43:56.624Z", "modified": "2024-01-16T13:48:33.819Z"}, {"entity": "publication", "iuid": "8f4af9fc1bd845f8bc456a6a13cd3e34", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8f4af9fc1bd845f8bc456a6a13cd3e34.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8f4af9fc1bd845f8bc456a6a13cd3e34"}}, "title": "Sensitive Detection of Cell-Free Tumour DNA Using Optimised Targeted Sequencing Can Predict Prognosis in Gastro-Oesophageal Cancer.", "authors": [{"family": "Wallander", "given": "Karin", "initials": "K", "orcid": "0000-0001-8166-9678", "researcher": {"href": "https://publications.scilifelab.se/researcher/db174787efd74dc1b84f1bf56b74a22d.json"}}, {"family": "Haider", "given": "Zahra", "initials": "Z", "orcid": "0000-0002-0759-3932", "researcher": {"href": "https://publications.scilifelab.se/researcher/4084e066170543e699dd116c8e7c05df.json"}}, {"family": "Jeggari", "given": "Ashwini", "initials": "A", "orcid": "0000-0002-7155-9050", "researcher": {"href": "https://publications.scilifelab.se/researcher/083131be9eab46df9c789fb018316dff.json"}}, {"family": "Foroughi-Asl", "given": "Hassan", "initials": "H"}, {"family": "Gellerbring", "given": "Anna", "initials": "A"}, {"family": "Lyander", "given": "Anna", "initials": "A"}, {"family": "Chozhan", "given": "Athithyan", "initials": "A"}, {"family": "Cuba Gyllensten", "given": "Ollanta", "initials": "O"}, {"family": "H\u00e4gglund", "given": "Moa", "initials": "M", "orcid": "0000-0003-3765-4342", "researcher": {"href": "https://publications.scilifelab.se/researcher/b3de7b5aa952454e81d0ff55056c33a0.json"}}, {"family": "Wirta", "given": "Valtteri", "initials": "V", "orcid": "0000-0003-3811-5439", "researcher": {"href": "https://publications.scilifelab.se/researcher/cba024b2e3c347f6b981922d984ad2d6.json"}}, {"family": "Nordenskj\u00f6ld", "given": "Magnus", "initials": "M"}, {"family": "Lindblad", "given": "Mats", "initials": "M"}, {"family": "Tham", "given": "Emma", "initials": "E", "orcid": "0000-0001-6079-164X", "researcher": {"href": "https://publications.scilifelab.se/researcher/6689dd9aff584082a57398141a538111.json"}}], "type": "journal article", "published": "2023-02-11", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "issn-l": "2072-6694", "volume": "15", "issue": "4", "pages": null}, "abstract": "In this longitudinal study, cell-free tumour DNA (a liquid biopsy) from plasma was explored as a prognostic biomarker for gastro-oesophageal cancer. Both tumour-informed and tumour-agnostic approaches for plasma variant filtering were evaluated in 47 participants. This was possible through sequencing of DNA from tissue biopsies from all participants and cell-free DNA from plasma sampled before and after surgery (n = 42), as well as DNA from white blood cells (n = 21) using a custom gene panel with and without unique molecular identifiers (UMIs). A subset of the plasma samples (n = 12) was also assayed with targeted droplet digital PCR (ddPCR). In 17/31 (55%) diagnostic plasma samples, tissue-verified cancer-associated variants could be detected by the gene panel. In the tumour-agnostic approach, 26 participants (59%) had cancer-associated variants, and UMIs were necessary to filter the true variants from the technical artefacts. Additionally, clonal haematopoietic variants could be excluded using the matched white blood cells or follow-up plasma samples. ddPCR detected its targets in 10/12 (83%) and provided an ultra-sensitive method for follow-up. Detectable cancer-associated variants in plasma correlated to a shorter overall survival and shorter time to progression, with a significant correlation for the tumour-informed approaches. In summary, liquid biopsy gene panel sequencing using a tumour-agnostic approach can be applied to all patients regardless of the presence of a tissue biopsy, although this requires UMIs and the exclusion of clonal haematopoietic variants. However, if sequencing data from tumour biopsies are available, a tumour-informed approach improves the value of cell-free tumour DNA as a negative prognostic biomarker in gastro-oesophageal cancer patients.", "doi": "10.3390/cancers15041160", "pmid": "36831507", "labels": {"Clinical Genomics Stockholm": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC9954085"}, {"db": "pii", "key": "cancers15041160"}], "notes": [], "created": "2023-11-22T21:52:05.588Z", "modified": "2023-11-22T21:52:13.584Z"}, {"entity": "publication", "iuid": "2faf5fd60f764dfa92d3120f79803dd2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2faf5fd60f764dfa92d3120f79803dd2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2faf5fd60f764dfa92d3120f79803dd2"}}, "title": "Immune-Activated B Cells Are Dominant in Prostate Cancer.", "authors": [{"family": "Saudi", "given": "Aws", "initials": "A"}, {"family": "Banday", "given": "Viqar", "initials": "V", "orcid": "0000-0002-5081-2272", "researcher": {"href": "https://publications.scilifelab.se/researcher/1e62d1e1569648a3905f3eb8b4d1469a.json"}}, {"family": "Zirakzadeh", "given": "A Ali", "initials": "AA", "orcid": "0000-0002-1568-1430", "researcher": {"href": "https://publications.scilifelab.se/researcher/2092f6ff059c465fb725d34f4640ff19.json"}}, {"family": "Selinger", "given": "Martin", "initials": "M", "orcid": "0000-0002-5420-9702", "researcher": {"href": "https://publications.scilifelab.se/researcher/fc68cdd8b8d748499e552a6e700d7e55.json"}}, {"family": "Forsberg", "given": "Jon", "initials": "J"}, {"family": "Holmbom", "given": "Martin", "initials": "M", "orcid": "0000-0002-3706-2294", "researcher": {"href": "https://publications.scilifelab.se/researcher/c0f3c0d388144a9d90b6f95e2f721f43.json"}}, {"family": "Henriksson", "given": "Johan", "initials": "J", "orcid": "0000-0002-7745-2844", "researcher": {"href": "https://publications.scilifelab.se/researcher/44339821900646b3881d4b4dfd09e8d5.json"}}, {"family": "Wald\u00e9n", "given": "Mauritz", "initials": "M"}, {"family": "Alamdari", "given": "Farhood", "initials": "F"}, {"family": "Aljabery", "given": "Firas", "initials": "F"}, {"family": "Winqvist", "given": "Ola", "initials": "O"}, {"family": "Sherif", "given": "Amir", "initials": "A", "orcid": "0000-0002-3675-3050", "researcher": {"href": "https://publications.scilifelab.se/researcher/e27ad5d3def147849d4821d86075c3d2.json"}}], "type": "journal article", "published": "2023-02-01", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "15", "issue": "3", "issn-l": "2072-6694"}, "abstract": "B cells are multifaceted immune cells responding robustly during immune surveillance against tumor antigens by presentation to T cells and switched immunoglobulin production. However, B cells are unstudied in prostate cancer (PCa). We used flow cytometry to analyze B-cell subpopulations in peripheral blood and lymph nodes from intermediate-high risk PCa patients. B-cell subpopulations were related to clinicopathological factors. B-cell-receptor single-cell sequencing and VDJ analysis identified clonal B-cell expansion in blood and lymph nodes. Pathological staging was pT2 in 16%, pT3a in 48%, and pT3b in 36%. Lymph node metastases occurred in 5/25 patients (20%). Compared to healthy donors, the peripheral blood CD19+ B-cell compartment was significantly decreased in PCa patients and dominated by na\u00efve B cells. The nodal B-cell compartment had significantly increased fractions of CD19+ B cells and switched memory B cells. Plasmablasts were observed in tumor-draining sentinel lymph nodes (SNs). VDJ analysis revealed clonal expansion in lymph nodes. Thus, activated B cells are increased in SNs from PCa patients. The increased fraction of switched memory cells and plasmablasts together with the presence of clonally expanded B cells indicate tumor-specific T-cell-dependent responses from B cells, supporting an important role for B cells in the protection against tumors.", "doi": "10.3390/cancers15030920", "pmid": "36765877", "labels": {"Clinical Genomics Ume\u00e5": "Service", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9913271"}, {"db": "pii", "key": "cancers15030920"}], "notes": [], "created": "2023-11-27T22:02:05.675Z", "modified": "2024-01-16T13:48:34.002Z"}, {"entity": "publication", "iuid": "0f4c992adb014d0c962a7a62313aed71", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0f4c992adb014d0c962a7a62313aed71.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0f4c992adb014d0c962a7a62313aed71"}}, "title": "Choice of High-Throughput Proteomics Method Affects Data Integration with Transcriptomics and the Potential Use in Biomarker Discovery.", "authors": [{"family": "Mosquim Junior", "given": "Sergio", "initials": "S", "orcid": "0000-0002-1537-7252", "researcher": {"href": "https://publications.scilifelab.se/researcher/1354a13a0b2f4a35865224291239e730.json"}}, {"family": "Siino", "given": "Valentina", "initials": "V", "orcid": "0000-0002-0489-6380", "researcher": {"href": "https://publications.scilifelab.se/researcher/04ca620e18e14085be456f76eb429902.json"}}, {"family": "Ryd\u00e9n", "given": "Lisa", "initials": "L", "orcid": "0000-0001-7515-3130", "researcher": {"href": "https://publications.scilifelab.se/researcher/424bace557344431a47ffe5cdccbeb56.json"}}, {"family": "Vallon-Christersson", "given": "Johan", "initials": "J", "orcid": "0000-0002-2195-0385", "researcher": {"href": "https://publications.scilifelab.se/researcher/648fa1d04cb640858fe3534d04cd04d1.json"}}, {"family": "Levander", "given": "Fredrik", "initials": "F", "orcid": "0000-0002-0710-9792", "researcher": {"href": "https://publications.scilifelab.se/researcher/1b7add45d810457eb84a72aebbc7b82c.json"}}], "type": "journal article", "published": "2022-11-23", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "14", "issue": "23", "issn-l": "2072-6694"}, "abstract": "In recent years, several advances have been achieved in breast cancer (BC) classification and treatment. However, overdiagnosis, overtreatment, and recurrent disease are still significant causes of complication and death. Here, we present the development of a protocol aimed at parallel transcriptome and proteome analysis of BC tissue samples using mass spectrometry, via Data Dependent and Independent Acquisitions (DDA and DIA). Protein digestion was semi-automated and performed on flowthroughs after RNA extraction. Data for 116 samples were acquired in DDA and DIA modes and processed using MaxQuant, EncyclopeDIA, or DIA-NN. DIA-NN showed an increased number of identified proteins, reproducibility, and correlation with matching RNA-seq data, therefore representing the best alternative for this setup. Gene Set Enrichment Analysis pointed towards complementary information being found between transcriptomic and proteomic data. A decision tree model, designed to predict the intrinsic subtypes based on differentially abundant proteins across different conditions, selected protein groups that recapitulate important clinical features, such as estrogen receptor status, HER2 status, proliferation, and aggressiveness. Taken together, our results indicate that the proposed protocol performed well for the application. Additionally, the relevance of the selected proteins points to the possibility of using such data as a biomarker discovery tool for personalized medicine.", "doi": "10.3390/cancers14235761", "pmid": "36497242", "labels": {"Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC9736226"}, {"db": "pii", "key": "cancers14235761"}], "notes": [], "created": "2023-09-27T07:00:02.527Z", "modified": "2023-09-27T07:00:02.646Z"}, {"entity": "publication", "iuid": "a148806847b9401f9686ddb8ca2bbb9c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a148806847b9401f9686ddb8ca2bbb9c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a148806847b9401f9686ddb8ca2bbb9c"}}, "title": "The Expression of the Immunoproteasome Subunit PSMB9 Is Related to Distinct Molecular Subtypes of Uterine Leiomyosarcoma.", "authors": [{"family": "Maia Falc\u00e3o", "given": "Raul", "initials": "R", "orcid": "0000-0003-3833-202X", "researcher": {"href": "https://publications.scilifelab.se/researcher/35ea8d57206e457aa24e93686de7ddb7.json"}}, {"family": "Kokaraki", "given": "Georgia", "initials": "G"}, {"family": "De Wispelaere", "given": "Wout", "initials": "W", "orcid": "0000-0002-7513-9002", "researcher": {"href": "https://publications.scilifelab.se/researcher/ade8b07417a94e729643d3d501c3154c.json"}}, {"family": "Amant", "given": "Fr\u00e9d\u00e9ric", "initials": "F", "orcid": "0000-0002-5452-4905", "researcher": {"href": "https://publications.scilifelab.se/researcher/cfe39e67b83d46d394cd087a39ebef39.json"}}, {"family": "De Souza", "given": "Gustavo Ant\u00f4nio", "initials": "GA"}, {"family": "de Souza", "given": "Jorge Estefano Santana", "initials": "JES"}, {"family": "Carlson", "given": "Joseph Woodward", "initials": "JW"}, {"family": "Petta", "given": "Tirzah Braz", "initials": "TB"}], "type": "journal article", "published": "2022-10-13", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "14", "issue": "20", "issn-l": "2072-6694"}, "abstract": "Uterine leiomyosarcoma (uLMS) are rare and malignant tumors that arise in the myometrium cells and whose diagnosis is based on histopathological features. Identifying diagnostic biomarkers for uLMS is a challenge due to molecular heterogeneity and the scarcity of samples. In vivo and in vitro models for uLMS are urgently needed. Knockout female mice for the catalytic subunit of the immunoproteasome PSMB9 (MIM:177045) develop spontaneous uLMS. This study aimed to analyze the role of PSMB9 in uLMS tumorigenesis and patient outcome.\n\nMolecular data from 3 non-related uLMS cohorts were integrated and analyzed by proteotranscriptomic using gene expression and protein abundance levels in 68 normal adjacent myometrium (MM), 66 uterine leiomyoma (LM), and 67 uLMS.\n\nthe immunoproteasome pathway is upregulated and the gene PMSB9 shows heterogeneous expression values in uLMS. Quartile group analysis showed no significant difference between groups high and low PSMB9 expression groups at 3-years overall survival (OS). Using CYBERSORTx analysis we observed 9 out of 17 samples in the high group clustering together due to high M2 macrophages and CD4 memory resting, and high CD8+/PSMB9 ratio was associated with better OS. The main pathway regulated in the high group is IFN\u03b3 and in the low is the ECM pathway dependent on the proto-oncogene SRC.\n\nthese findings suggest 2 subtypes of uLMS (immune-related and ECM-related) with different candidate mechanisms of malignancy.", "doi": "10.3390/cancers14205007", "pmid": "36291793", "labels": {"Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9600211"}, {"db": "pii", "key": "cancers14205007"}], "notes": [], "created": "2022-11-24T21:12:37.555Z", "modified": "2022-11-24T21:12:37.674Z"}, {"entity": "publication", "iuid": "f5a81fbb0cbc43fabca9d5298e78e612", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f5a81fbb0cbc43fabca9d5298e78e612.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f5a81fbb0cbc43fabca9d5298e78e612"}}, "title": "Synergistic Effects of Sanglifehrin-Based Cyclophilin Inhibitor NV651 with Cisplatin in Hepatocellular Carcinoma.", "authors": [{"family": "Sim\u00f3n Serrano", "given": "Sonia", "initials": "S", "orcid": "0000-0002-0166-0006", "researcher": {"href": "https://publications.scilifelab.se/researcher/6e5c20f8789e40a299bfafa41129f999.json"}}, {"family": "Tavecchio", "given": "Michele", "initials": "M"}, {"family": "Mallik", "given": "Josef", "initials": "J"}, {"family": "Gr\u00f6nberg", "given": "Alvar", "initials": "A"}, {"family": "Elm\u00e9r", "given": "Eskil", "initials": "E", "orcid": "0000-0001-7901-1826", "researcher": {"href": "https://publications.scilifelab.se/researcher/8313ce5e20504a33822e0e4ff2faf46a.json"}}, {"family": "Kifagi", "given": "Chamseddine", "initials": "C", "orcid": "0000-0002-3744-5228", "researcher": {"href": "https://publications.scilifelab.se/researcher/47289b6fbb5740089077a49a9a9eb4e7.json"}}, {"family": "Gallay", "given": "Philippe", "initials": "P"}, {"family": "Hansson", "given": "Magnus Joakim", "initials": "MJ"}, {"family": "Massoumi", "given": "Ramin", "initials": "R", "orcid": "0000-0001-8875-6440", "researcher": {"href": "https://publications.scilifelab.se/researcher/c019a5eed3144760b8c55badc75280f7.json"}}], "type": "journal article", "published": "2022-09-20", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "14", "issue": "19", "pages": "4553", "issn-l": "2072-6694"}, "abstract": "Hepatocellular carcinoma (HCC), commonly diagnosed at an advanced stage, is the most common primary liver cancer. Owing to a lack of effective HCC treatments and the commonly acquired chemoresistance, novel therapies need to be investigated. Cyclophilins-intracellular proteins with peptidyl-prolyl isomerase activity-have been shown to play a key role in therapy resistance and cell proliferation. Here, we aimed to evaluate changes in the gene expression of HCC cells caused by cyclophilin inhibition in order to explore suitable combination treatment approaches, including the use of chemoagents, such as cisplatin. Our results show that the novel cyclophilin inhibitor NV651 decreases the expression of genes involved in several pathways related to the cancer cell cycle and DNA repair. We evaluated the potential synergistic effect of NV651 in combination with other treatments used against HCC in cisplatin-sensitive cells. NV651 showed a synergistic effect in inhibiting cell proliferation, with a significant increase in intrinsic apoptosis in combination with the DNA crosslinking agent cisplatin. This combination also affected cell cycle progression and reduced the capacity of the cell to repair DNA in comparison with a single treatment with cisplatin. Based on these results, we believe that the combination of cisplatin and NV651 may provide a novel approach to HCC treatment.", "doi": "10.3390/cancers14194553", "pmid": "36230472", "labels": {"Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics Support and Infrastructure": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9559492"}, {"db": "pii", "key": "cancers14194553"}], "notes": [], "created": "2022-09-29T07:03:35.075Z", "modified": "2023-06-02T10:28:13.887Z"}, {"entity": "publication", "iuid": "ae81f81f52cb4fbc9ea20d482d20a8b6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ae81f81f52cb4fbc9ea20d482d20a8b6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ae81f81f52cb4fbc9ea20d482d20a8b6"}}, "title": "Proliferation and Immune Response Gene Signatures Associated with Clinical Outcome to Immunotherapy and Targeted Therapy in Metastatic Cutaneous Malignant Melanoma.", "authors": [{"family": "Costa Svedman", "given": "Fernanda", "initials": "F", "orcid": "0000-0001-8065-3375", "researcher": {"href": "https://publications.scilifelab.se/researcher/468b2e407aeb49a88b1ef0f7b1e02ce7.json"}}, {"family": "Das", "given": "Ishani", "initials": "I"}, {"family": "Tuominen", "given": "Rainer", "initials": "R"}, {"family": "Darai Ramqvist", "given": "Eva", "initials": "E"}, {"family": "H\u00f6iom", "given": "Veronica", "initials": "V"}, {"family": "Egyhazi Brage", "given": "Suzanne", "initials": "S"}], "type": "journal article", "published": "2022-07-22", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "14", "issue": "15", "issn-l": "2072-6694"}, "abstract": "Targeted therapy (TT), together with immune checkpoint inhibitors (ICI), has significantly improved clinical outcomes for patients with advanced cutaneous malignant melanoma (CMM) during the last decade. However, the magnitude and the duration of response vary considerably. There is still a paucity of predictive biomarkers to identify patients who benefit most from treatment. To address this, we performed targeted transcriptomics of CMM tumors to identify biomarkers associated with clinical outcomes. Pre-treatment tumor samples from 28 patients with advanced CMM receiving TT (n = 13) or ICI (n = 15) were included in the study. Targeted RNA sequencing was performed using Ion AmpliSeq \u2122, followed by gene set enrichment analysis (GSEA) using MSigDB's Hallmark Gene Set Collection to identify gene expression signatures correlating with treatment outcome. The GSEA demonstrated that up-regulation of allograft rejection genes, together with down-regulation of E2F and MYC targets as well as G2M checkpoint genes, significantly correlated with longer progression-free survival on ICI while IFN\u03b3 and inflammatory response genes were associated with a better clinical outcome on TT. In conclusion, we identify novel genes and their expression signatures as potential predictive biomarkers for TT and ICI in patients with metastatic CMM, paving the way for clinical use following larger validation studies.", "doi": "10.3390/cancers14153587", "pmid": "35892846", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "NGI Short read": "Service"}, "xrefs": [{"db": "pii", "key": "cancers14153587"}, {"db": "pmc", "key": "PMC9331037"}], "notes": [], "created": "2022-09-05T07:12:08.602Z", "modified": "2022-09-05T07:12:08.643Z"}, {"entity": "publication", "iuid": "84a78d53a4334fc19fc2291e44e6e963", "links": {"self": {"href": "https://publications.scilifelab.se/publication/84a78d53a4334fc19fc2291e44e6e963.json"}, "display": {"href": "https://publications.scilifelab.se/publication/84a78d53a4334fc19fc2291e44e6e963"}}, "title": "Next Generation Plasma Proteomics Identifies High-Precision Biomarker Candidates for Ovarian Cancer.", "authors": [{"family": "Gyllensten", "given": "Ulf", "initials": "U"}, {"family": "Hedlund-Lindberg", "given": "Julia", "initials": "J"}, {"family": "Svensson", "given": "Johanna", "initials": "J"}, {"family": "Manninen", "given": "Johanna", "initials": "J"}, {"family": "\u00d6st", "given": "Torbj\u00f6rn", "initials": "T"}, {"family": "Ramsell", "given": "Jon", "initials": "J"}, {"family": "\u00c5slin", "given": "Matilda", "initials": "M", "orcid": "0000-0002-2450-6415", "researcher": {"href": "https://publications.scilifelab.se/researcher/f3f0bf2483a543d689fb6e95804066dd.json"}}, {"family": "Ivansson", "given": "Emma", "initials": "E"}, {"family": "Lomnytska", "given": "Marta", "initials": "M"}, {"family": "Lycke", "given": "Maria", "initials": "M"}, {"family": "Axelsson", "given": "Tomas", "initials": "T"}, {"family": "Liljedahl", "given": "Ulrika", "initials": "U"}, {"family": "Nordlund", "given": "Jessica", "initials": "J", "orcid": "0000-0001-8699-9959", "researcher": {"href": "https://publications.scilifelab.se/researcher/ddf48c9262134821bcc6ce1180049753.json"}}, {"family": "Edqvist", "given": "Per-Henrik", "initials": "PH", "orcid": "0000-0002-8330-0134", "researcher": {"href": "https://publications.scilifelab.se/researcher/dd5ff31463cd4345a1fc8351e797ac7f.json"}}, {"family": "Sj\u00f6blom", "given": "Tobias", "initials": "T", "orcid": "0000-0001-6668-4140", "researcher": {"href": "https://publications.scilifelab.se/researcher/909f00a5bf6e465f9ff560b12bcd863a.json"}}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M"}, {"family": "St\u00e5lberg", "given": "Karin", "initials": "K", "orcid": "0000-0001-5527-8796", "researcher": {"href": "https://publications.scilifelab.se/researcher/47a9c8e243994dccb4730266b0431d6d.json"}}, {"family": "Sundfeldt", "given": "Karin", "initials": "K", "orcid": "0000-0002-7135-3132", "researcher": {"href": "https://publications.scilifelab.se/researcher/fb40cfcba9154502ad1d530c5e4a8a66.json"}}, {"family": "\u00c5berg", "given": "Mikael", "initials": "M"}, {"family": "Enroth", "given": "Stefan", "initials": "S", "orcid": "0000-0002-5056-9137", "researcher": {"href": "https://publications.scilifelab.se/researcher/16bb97ef16ee49f3ae0c7ea0495fd971.json"}}], "type": "journal article", "published": "2022-03-30", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "14", "issue": "7", "issn-l": "2072-6694"}, "abstract": "Ovarian cancer is the eighth most common cancer among women and has a 5-year survival of only 30-50%. The survival is close to 90% for patients in stage I but only 20% for patients in stage IV. The presently available biomarkers have insufficient sensitivity and specificity for early detection and there is an urgent need to identify novel biomarkers.\n\nWe employed the Explore PEA technology for high-precision analysis of 1463 plasma proteins and conducted a discovery and replication study using two clinical cohorts of previously untreated patients with benign or malignant ovarian tumours (N = 111 and N = 37).\n\nThe discovery analysis identified 32 proteins that had significantly higher levels in malignant cases as compared to benign diagnoses, and for 28 of these, the association was replicated in the second cohort. Multivariate modelling identified three highly accurate models based on 4 to 7 proteins each for separating benign tumours from early-stage and/or late-stage ovarian cancers, all with AUCs above 0.96 in the replication cohort. We also developed a model for separating the early-stage from the late-stage achieving an AUC of 0.81 in the replication cohort. These models were based on eleven proteins in total (ALPP, CXCL8, DPY30, IL6, IL12, KRT19, PAEP, TSPAN1, SIGLEC5, VTCN1, and WFDC2), notably without MUCIN-16. The majority of the associated proteins have been connected to ovarian cancer but not identified as potential biomarkers.\n\nThe results show the ability of using high-precision proteomics for the identification of novel plasma protein biomarker candidates for the early detection of ovarian cancer.", "doi": "10.3390/cancers14071757", "pmid": "35406529", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Proteomics": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Collaborative", "Affinity Proteomics Uppsala": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC8997113"}, {"db": "pii", "key": "cancers14071757"}], "notes": [], "created": "2022-05-06T10:19:41.790Z", "modified": "2022-12-02T08:50:06.321Z"}, {"entity": "publication", "iuid": "01b396ca14784d979d8f1a5282eb9c7c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/01b396ca14784d979d8f1a5282eb9c7c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/01b396ca14784d979d8f1a5282eb9c7c"}}, "title": "Downregulation and Hypermethylation of GABPB1 Is Associated with Aggressive Thyroid Cancer Features.", "authors": [{"family": "Xing", "given": "Xiangling", "initials": "X"}, {"family": "Mu", "given": "Ninni", "initials": "N", "orcid": "0000-0002-3887-880X", "researcher": {"href": "https://publications.scilifelab.se/researcher/b478578ad34b40ecb865f915e86e59b6.json"}}, {"family": "Yuan", "given": "Xiaotian", "initials": "X", "orcid": "0000-0002-1501-518X", "researcher": {"href": "https://publications.scilifelab.se/researcher/00b10c4020514185be7da4077f78e4f2.json"}}, {"family": "Wang", "given": "Na", "initials": "N"}, {"family": "Juhlin", "given": "C Christofer", "initials": "CC", "orcid": "0000-0002-5945-9081", "researcher": {"href": "https://publications.scilifelab.se/researcher/bb660e24421749d4acaaf6e9a90042f8.json"}}, {"family": "Str\u00e5\u00e5t", "given": "Klas", "initials": "K"}, {"family": "Larsson", "given": "Catharina", "initials": "C"}, {"family": "Neo", "given": "Shi Yong", "initials": "SY"}, {"family": "Xu", "given": "Dawei", "initials": "D", "orcid": "0000-0003-3141-4524", "researcher": {"href": "https://publications.scilifelab.se/researcher/a90bfbbe83364a1087de699dc3b4b80c.json"}}], "type": "journal article", "published": "2022-03-08", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "issn-l": "2072-6694", "volume": "14", "issue": "6", "pages": null}, "abstract": "Promoter mutations of the telomerase reverse transcriptase (TERT) gene occur frequently in thyroid carcinoma (TC), including papillary (PTC) and anaplastic subtypes (ATC). Given that the ETS family transcription factors GABPA and GABPB1 activate the mutant TERT promoter and induce TERT expression for telomerase activation, GABPB1 has been proposed as a cancer therapeutic target to inhibit telomerase. Here, we sought to determine the role of GABPB1 in TC pathogenesis. In TC-derived cells carrying the mutated TERT promoter, GABPB1 knockdown led to diminished TERT expression but significantly increased invasive potentials in vitro and metastatic potential in a xenograft zebrafish model and altered expression of markers for epithelial-to-mesenchymal transition. GABPB1 expression was downregulated in aggressive TCs. Low GABPB1 expression correlated with its promoter hypermethylation, which in turn was also associated with shorter disease-free survival. Consistently, DNA methylation inhibitors enhanced GABPB1 expression, as observed upon reduced promoter methylation. Our results suggest that GABPB1 is required for TERT expression and telomerase activation, but itself serves as a tumor suppressor to inhibit TC progression. Furthermore, aberrant DNA methylation leads to GABPB1 silencing, thereby promoting TC aggressiveness. Thus, caution is needed if targeting GABPB1 for cancer therapy is considered.", "doi": "10.3390/cancers14061385", "pmid": "35326537", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Short read": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8946831"}, {"db": "pii", "key": "cancers14061385"}], "notes": [], "created": "2023-01-13T12:59:08.053Z", "modified": "2024-01-02T13:08:48.641Z"}, {"entity": "publication", "iuid": "9591fd31f8354bb68ebb9e31259336ef", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9591fd31f8354bb68ebb9e31259336ef.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9591fd31f8354bb68ebb9e31259336ef"}}, "title": "Genetic Alterations in Mitochondrial DNA Are Complementary to Nuclear DNA Mutations in Pheochromocytomas.", "authors": [{"family": "Tabebi", "given": "Mouna", "initials": "M", "orcid": "0000-0002-2873-161X", "researcher": {"href": "https://publications.scilifelab.se/researcher/285705c043f34b55826e7f33ab36a875.json"}}, {"family": "\u0141ysiak", "given": "Ma\u0142gorzata", "initials": "M", "orcid": "0000-0002-0244-759X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7f5d37e79764c31a5a0a421c34ed1a8.json"}}, {"family": "Dutta", "given": "Ravi Kumar", "initials": "RK"}, {"family": "Lomazzi", "given": "Sandra", "initials": "S"}, {"family": "Turkina", "given": "Maria V", "initials": "MV"}, {"family": "Brunaud", "given": "Laurent", "initials": "L", "orcid": "0000-0001-5182-6660", "researcher": {"href": "https://publications.scilifelab.se/researcher/132c416fbbde4a1f90d4a8c0e95f9f1f.json"}}, {"family": "Gimm", "given": "Oliver", "initials": "O", "orcid": "0000-0002-0054-664X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9879641fb40042ae90ff034f4912a16d.json"}}, {"family": "S\u00f6derkvist", "given": "Peter", "initials": "P"}], "type": "journal article", "published": "2022-01-06", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "14", "issue": "2", "issn-l": "2072-6694"}, "abstract": "Somatic mutations, copy-number variations, and genome instability of mitochondrial DNA (mtDNA) have been reported in different types of cancers and are suggested to play important roles in cancer development and metastasis. However, there is scarce information about pheochromocytomas and paragangliomas (PCCs/PGLs) formation.\n\nTo determine the potential roles of mtDNA alterations in sporadic PCCs/PGLs, we analyzed a panel of 26 nuclear susceptibility genes and the entire mtDNA sequence of seventy-seven human tumors, using next-generation sequencing, and compared the results with normal adrenal medulla tissues. We also performed an analysis of copy-number alterations, large mtDNA deletion, and gene and protein expression.\n\nOur results revealed that 53.2% of the tumors harbor a mutation in at least one of the targeted susceptibility genes, and 16.9% harbor complementary mitochondrial mutations. More than 50% of the mitochondrial mutations were novel and predicted pathogenic, affecting mitochondrial oxidative phosphorylation. Large deletions were found in 26% of tumors, and depletion of mtDNA occurred in more than 87% of PCCs/PGLs. The reduction of the mitochondrial number was accompanied by a reduced expression of the regulators that promote mitochondrial biogenesis (PCG1\u03b1, NRF1, and TFAM). Further, P62 and LC3a gene expression suggested increased mitophagy, which is linked to mitochondrial dysfunction.\n\nThe pathogenic role of these finding remains to be shown, but we suggest a complementarity and a potential contributing role in PCCs/PGLs tumorigenesis.", "doi": "10.3390/cancers14020269", "pmid": "35053433", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8773562"}, {"db": "pii", "key": "cancers14020269"}], "notes": [], "created": "2022-12-01T14:13:42.523Z", "modified": "2022-12-01T14:13:42.606Z"}, {"entity": "publication", "iuid": "77a6fcbf80d74953b0f9c1b7234a221d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/77a6fcbf80d74953b0f9c1b7234a221d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/77a6fcbf80d74953b0f9c1b7234a221d"}}, "title": "Whole-Exome Sequencing of HPV Positive Tonsillar and Base of Tongue Squamous Cell Carcinomas Reveals a Global Mutational Pattern along with Relapse-Specific Somatic Variants.", "authors": [{"family": "\u00c4hrlund-Richter", "given": "Andreas", "initials": "A"}, {"family": "Holzhauser", "given": "Stefan", "initials": "S"}, {"family": "Dalianis", "given": "Tina", "initials": "T"}, {"family": "N\u00e4sman", "given": "Anders", "initials": "A", "orcid": "0000-0003-4602-4297", "researcher": {"href": "https://publications.scilifelab.se/researcher/368352486dc54915b6873ad1aae59ea2.json"}}, {"family": "Mints", "given": "Michael", "initials": "M"}], "type": "journal article", "published": "2021-12-24", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "14", "issue": "1", "issn-l": "2072-6694"}, "abstract": "To identify predictive/targetable markers in human papillomavirus positive (HPV+) tonsillar and base of tongue cancer (TSCC/BOTSCC), whole-exome sequencing (WES) of tumours of patients with/without recurrence was performed. Forty primary tumours and adjacent normal tissue were separated by micro-dissection from formalin-fixed paraffin-embedded tissue from patients treated with curative intent 2000-2014 at Karolinska University Hospital. Successful sequencing was obtained in primary tumours of 18 patients without and primaries of 17 with local or distant recurrence, as well as in 10 corresponding recurrences (i.e., five local relapses and five distant metastases) from these 17 patients. One variant-a high-impact deletion in the CDC27 gene-was observed only in primaries of 5/17 patients that had a recurrence after full treatment but in none of those without recurrence. In addition, 3 variants and 26 mutated genes, including CDC27, BCLAF1 and AQP7, were present in at least 30% of all primary tumours independent of prognosis. To conclude, a CDC27 deletion was specific and found in ~30% of samples from patients with a local relapse/distant metastasis and could, therefore, potentially be a prospective marker to predict prognosis. Commonly mutated genes, such as BCLAF1, should be further studied in the context of targeted therapy.", "doi": "10.3390/cancers14010077", "pmid": "35008243", "labels": {"Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics Support and Infrastructure": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pii", "key": "cancers14010077"}, {"db": "pmc", "key": "PMC8750256"}], "notes": [], "created": "2022-01-17T08:37:22.165Z", "modified": "2022-01-17T08:37:22.180Z"}, {"entity": "publication", "iuid": "fd32a79bac2c4dec8dc43e60bcd060f0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fd32a79bac2c4dec8dc43e60bcd060f0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fd32a79bac2c4dec8dc43e60bcd060f0"}}, "title": "Immune-Proteome Profiling in Classical Hodgkin Lymphoma Tumor Diagnostic Tissue.", "authors": [{"family": "Gholiha", "given": "Alex Reza", "initials": "AR", "orcid": "0000-0002-3393-1106", "researcher": {"href": "https://publications.scilifelab.se/researcher/727d46bb6742412aacdf87a38957b3e9.json"}}, {"family": "Hollander", "given": "Peter", "initials": "P", "orcid": "0000-0002-0226-5681", "researcher": {"href": "https://publications.scilifelab.se/researcher/b1c6693d3ede463eb78e6da010db601f.json"}}, {"family": "L\u00f6f", "given": "Liza", "initials": "L"}, {"family": "Larsson", "given": "Anders", "initials": "A", "orcid": "0000-0003-3161-0402", "researcher": {"href": "https://publications.scilifelab.se/researcher/2276de26382b402aa384ac231f30f156.json"}}, {"family": "Hashemi", "given": "Jamileh", "initials": "J"}, {"family": "Ulfstedt", "given": "Johan Mattsson", "initials": "JM", "orcid": "0000-0003-0682-7394", "researcher": {"href": "https://publications.scilifelab.se/researcher/d97878de79294d14b317f56f7bbf774c.json"}}, {"family": "Molin", "given": "Daniel", "initials": "D"}, {"family": "Amini", "given": "Rose-Marie", "initials": "RM"}, {"family": "Freyhult", "given": "Eva", "initials": "E", "orcid": "0000-0003-0226-1047", "researcher": {"href": "https://publications.scilifelab.se/researcher/be110f11a53d4dcfa3bfd1657167895e.json"}}, {"family": "Kamali-Moghaddam", "given": "Masood", "initials": "M"}, {"family": "Enblad", "given": "Gunilla", "initials": "G"}], "type": "journal article", "published": "2021-12-21", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "14", "issue": "1", "pages": "9", "issn-l": "2072-6694"}, "abstract": "In classical Hodgkin Lymphoma (cHL), immunoediting via protein signaling is key to evading tumor surveillance. We aimed to identify immune-related proteins that distinguish diagnostic cHL tissues (=diagnostic tumor lysates, n = 27) from control tissues (reactive lymph node lysates, n = 30). Further, we correlated our findings with the proteome plasma profile between cHL patients (n = 26) and healthy controls (n = 27). We used the proximity extension assay (PEA) with the OlinkTM multiplex Immuno-Oncology panel, consisting of 92 proteins. Univariate, multivariate-adjusted analysis and Benjamini-Hochberg's false discovery testing (=Padj) were performed to detect significant discrepancies. Proteins distinguishing cHL cases from controls were more numerous in plasma (30 proteins) than tissue (17 proteins), all Padj < 0.05. Eight of the identified proteins in cHL tissue (PD-L1, IL-6, CCL17, CCL3, IL-13, MMP12, TNFRS4, and LAG3) were elevated in both cHL tissues and cHL plasma compared with control samples. Six proteins distinguishing cHL tissues from controls tissues were significantly correlated to PD-L1 expression in cHL tissue (IL-6, MCP-2, CCL3, CCL4, GZMB, and IFN-gamma, all p \u22640.05). In conclusion, this study introduces a distinguishing proteomic profile in cHL tissue and potential immune-related markers of pathophysiological relevance.", "doi": "10.3390/cancers14010009", "pmid": "35008176", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "cancers14010009"}, {"db": "pmc", "key": "PMC8750205"}], "notes": [], "created": "2022-01-11T07:52:22.416Z", "modified": "2022-11-21T15:22:11.449Z"}, {"entity": "publication", "iuid": "d174e3174b0a40048a8077f2f8ee7d24", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d174e3174b0a40048a8077f2f8ee7d24.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d174e3174b0a40048a8077f2f8ee7d24"}}, "title": "Changes in the Proteome in the Development of Chronic Human Papillomavirus Infection-A Prospective Study in HIV Positive and HIV Negative Rwandan Women.", "authors": [{"family": "Bienvenu", "given": "Emile", "initials": "E"}, {"family": "Mukanyangezi", "given": "Marie Francoise", "initials": "MF"}, {"family": "Rulisa", "given": "Stephen", "initials": "S"}, {"family": "Martner", "given": "Anna", "initials": "A", "orcid": "0000-0002-6598-5221", "researcher": {"href": "https://publications.scilifelab.se/researcher/7cd028aac9124c4098a9bbc033affe6e.json"}}, {"family": "Hass\u00e9us", "given": "Bengt", "initials": "B"}, {"family": "Vorontsov", "given": "Egor", "initials": "E"}, {"family": "Tobin", "given": "Gunnar", "initials": "G"}, {"family": "Giglio", "given": "Daniel", "initials": "D", "orcid": "0000-0002-1349-9336", "researcher": {"href": "https://publications.scilifelab.se/researcher/5bde1c5f1cfd42df988ca7353a800ecb.json"}}], "type": "journal article", "published": "2021-11-28", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "13", "issue": "23", "issn-l": "2072-6694"}, "abstract": "Effects on the proteome when a high risk (HR)-HPV infection occurs, when it is cleared and when it becomes chronic were investigated. Moreover, biomarker panels that could identify cervical risk lesions were assessed.\n\nCytology, HPV screening and proteomics were performed on cervical samples from Rwandan HIV+ and HIV- women at baseline, at 9 months, at 18 months and at 24 months. Biological pathways were identified using the String database.\n\nThe most significantly affected pathway when an incident HR-HPV infection occurred was neutrophil degranulation, and vesicle-mediated transport was the most significantly affected pathway when an HR-HPV infection was cleared; protein insertion into membrane in chronic HR-HPV lesions and in lesions where HR-HPVs were cleared were compared; and cellular catabolic process in high-grade lesions was compared to that in negative lesions. A four-biomarker panel (EIF1; BLOC1S5; LIMCH1; SGTA) was identified, which was able to distinguish chronic HR-HPV lesions from cleared HR-HPV/negative lesions (sensitivity 100% and specificity 91%). Another four-biomarker panel (ERH; IGKV2-30; TMEM97; DNAJA4) was identified, which was able to distinguish high-grade lesions from low-grade/negative lesions (sensitivity 100% and specificity 81%).\n\nWe have identified the biological pathways triggered in HR-HPV infection, when HR-HPV becomes chronic and when cervical risk lesions develop. Moreover, we have identified potential biomarkers that may help to identify women with cervical risk lesions.", "doi": "10.3390/cancers13235983", "pmid": "34885095", "labels": {"Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8656715"}, {"db": "pii", "key": "cancers13235983"}], "notes": [], "created": "2023-03-07T14:36:26.067Z", "modified": "2024-01-16T13:46:29.788Z"}, {"entity": "publication", "iuid": "92916c7849ec4651b0b9ec3d10f0581a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/92916c7849ec4651b0b9ec3d10f0581a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/92916c7849ec4651b0b9ec3d10f0581a"}}, "title": "Tonsillar Cancer with High CD8+ T-Cell Infiltration Features Increased Levels of Dendritic Cells and Transcriptional Regulation Associated with an Inflamed Tumor Microenvironment.", "authors": [{"family": "Jimenez", "given": "David Gomez", "initials": "DG"}, {"family": "Sobti", "given": "Aastha", "initials": "A"}, {"family": "Askmyr", "given": "David", "initials": "D", "orcid": "0000-0003-1312-8524", "researcher": {"href": "https://publications.scilifelab.se/researcher/0249a39d931d4f5198312aa3125a105d.json"}}, {"family": "Sakellariou", "given": "Christina", "initials": "C"}, {"family": "Santos", "given": "Sofia Carreira", "initials": "SC"}, {"family": "Swoboda", "given": "Sabine", "initials": "S"}, {"family": "Forslund", "given": "Ola", "initials": "O"}, {"family": "Greiff", "given": "Lennart", "initials": "L"}, {"family": "Lindstedt", "given": "Malin", "initials": "M"}], "type": "journal article", "published": "2021-10-25", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "13", "issue": "21", "issn-l": "2072-6694"}, "abstract": "Human papillomavirus (HPV) is the main causal agent of tonsillar cancer (TC) and HPV+ TC has a favorable prognosis compared to HPV- disease. In this study, we examined aspects of the tumor microenvironment of TC, focusing on T-cells, dendritic cells (DC), and macrophages. Fresh biopsies of TC and the contralateral healthy tonsil (HT) were obtained from 20 patients, analyzed by multiparameter flow cytometry, and assessed against a detailed HPV-status. Additionally, RNA-sequencing data from 38 TC samples available in the public database, The Cancer Genome Atlas (TCGA), were explored, focusing on the same leukocyte populations. HPV+ TC featured increased levels of CD8+ T-cells and antigen-presenting cells (cf. HPV- TC and HT, respectively). In HPV+ TC, CD8+ T-cell frequencies correlated to DC levels independently of tumor stage, HPV 16 copy number, and E7 oncogene expression as well as frequencies of other leukocytes. Similarly, RNA sequencing data were explored by dividing the HPV+ TCs according to predefined CD8+ T-cell scores in silico. Higher levels of genes expressed by antigen-presenting cells and effector T-cells, such as immune checkpoints and cytokines, were detected in the CD8HIGH HPV+ TC samples (cf. CD8LOW HPV+ TC). In conclusion, CD8HIGH HPV+ TC displays a unique inflammatory profile associated with increased effector T-cell functions and the presence of antigen-presenting cells in the tumor microenvironment. Further studies are warranted to assess if this information can be used on an individual basis to aid in prognosis and treatment decisions.", "doi": "10.3390/cancers13215341", "pmid": "34771506", "labels": {"Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics Support and Infrastructure": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pii", "key": "cancers13215341"}, {"db": "pmc", "key": "PMC8582523"}], "notes": [], "created": "2021-12-02T13:59:26.828Z", "modified": "2021-12-02T13:59:26.872Z"}, {"entity": "publication", "iuid": "2071a85470314d6c85780a70fdddb53a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2071a85470314d6c85780a70fdddb53a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2071a85470314d6c85780a70fdddb53a"}}, "title": "Morphological Features Extracted by AI Associated with Spatial Transcriptomics in Prostate Cancer.", "authors": [{"family": "Chelebian", "given": "Eduard", "initials": "E", "orcid": "0000-0001-6852-6605", "researcher": {"href": "https://publications.scilifelab.se/researcher/278694af6d7e499f9432c6523da24f25.json"}}, {"family": "Avenel", "given": "Christophe", "initials": "C", "orcid": "0000-0002-1835-921X", "researcher": {"href": "https://publications.scilifelab.se/researcher/5471168acdf94b63b1eab431fd1e8442.json"}}, {"family": "Kartasalo", "given": "Kimmo", "initials": "K", "orcid": "0000-0002-9470-4783", "researcher": {"href": "https://publications.scilifelab.se/researcher/da3da754a0264d538a98d8a85874aec1.json"}}, {"family": "Marklund", "given": "Maja", "initials": "M", "orcid": "0000-0003-2627-2437", "researcher": {"href": "https://publications.scilifelab.se/researcher/6a238f7adbc242398a46fd24190a2811.json"}}, {"family": "Tanoglidi", "given": "Anna", "initials": "A", "orcid": "0000-0002-1217-2219", "researcher": {"href": "https://publications.scilifelab.se/researcher/86fcef314379488ba7750f581f4ec5f6.json"}}, {"family": "Mirtti", "given": "Tuomas", "initials": "T", "orcid": "0000-0003-0455-9891", "researcher": {"href": "https://publications.scilifelab.se/researcher/53407e73bd7945af87fcd3b8718fbf4d.json"}}, {"family": "Colling", "given": "Richard", "initials": "R", "orcid": "0000-0001-6344-9081", "researcher": {"href": "https://publications.scilifelab.se/researcher/e817042b24944db1b2fcf74aee34f4e3.json"}}, {"family": "Erickson", "given": "Andrew", "initials": "A", "orcid": "0000-0002-4850-4086", "researcher": {"href": "https://publications.scilifelab.se/researcher/adfe533187e645afa52b17e1f053a82e.json"}}, {"family": "Lamb", "given": "Alastair D", "initials": "AD", "orcid": "0000-0002-2968-7155", "researcher": {"href": "https://publications.scilifelab.se/researcher/798d88b3df1e4a7d994e90b5d60372e6.json"}}, {"family": "Lundeberg", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4313-1601", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a4e6ca0f29b4ead8569e2729481c3e0.json"}}, {"family": "W\u00e4hlby", "given": "Carolina", "initials": "C", "orcid": "0000-0002-4139-7003", "researcher": {"href": "https://publications.scilifelab.se/researcher/c50194fbc8524d95b7152663ccf17f29.json"}}], "type": "journal article", "published": "2021-09-28", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "13", "issue": "19", "issn-l": "2072-6694"}, "abstract": "Prostate cancer is a common cancer type in men, yet some of its traits are still under-explored. One reason for this is high molecular and morphological heterogeneity. The purpose of this study was to develop a method to gain new insights into the connection between morphological changes and underlying molecular patterns. We used artificial intelligence (AI) to analyze the morphology of seven hematoxylin and eosin (H&E)-stained prostatectomy slides from a patient with multi-focal prostate cancer. We also paired the slides with spatially resolved expression for thousands of genes obtained by a novel spatial transcriptomics (ST) technique. As both spaces are highly dimensional, we focused on dimensionality reduction before seeking associations between them. Consequently, we extracted morphological features from H&E images using an ensemble of pre-trained convolutional neural networks and proposed a workflow for dimensionality reduction. To summarize the ST data into genetic profiles, we used a previously proposed factor analysis. We found that the regions were automatically defined, outlined by unsupervised clustering, associated with independent manual annotations, in some cases, finding further relevant subdivisions. The morphological patterns were also correlated with molecular profiles and could predict the spatial variation of individual genes. This novel approach enables flexible unsupervised studies relating morphological and genetic heterogeneity using AI to be carried out.", "doi": "10.3390/cancers13194837", "pmid": "34638322", "labels": {"BioImage Informatics": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "cancers13194837"}, {"db": "pmc", "key": "PMC8507756"}], "notes": [], "created": "2021-11-29T12:38:38.795Z", "modified": "2022-11-02T06:15:40.497Z"}, {"entity": "publication", "iuid": "70634ed7773f4b04ad1654c58b5c6afd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/70634ed7773f4b04ad1654c58b5c6afd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/70634ed7773f4b04ad1654c58b5c6afd"}}, "title": "Therapeutic Cancer Vaccination with Immunopeptidomics-Discovered Antigens Confers Protective Antitumor Efficacy.", "authors": [{"family": "Peltonen", "given": "Karita", "initials": "K", "orcid": "0000-0002-3063-451X", "researcher": {"href": "https://publications.scilifelab.se/researcher/32560e34c90144a4803499ee8d5e6efe.json"}}, {"family": "Feola", "given": "Sara", "initials": "S", "orcid": "0000-0002-4012-4310", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9d2c4168aa541b5ad9a7e5155dc1069.json"}}, {"family": "Umer", "given": "Husen M", "initials": "HM"}, {"family": "Chiaro", "given": "Jacopo", "initials": "J"}, {"family": "Mermelekas", "given": "Georgios", "initials": "G"}, {"family": "Yl\u00f6sm\u00e4ki", "given": "Erkko", "initials": "E", "orcid": "0000-0001-9678-2614", "researcher": {"href": "https://publications.scilifelab.se/researcher/14a39635a8c14adb86ec2d63e23500b6.json"}}, {"family": "Pesonen", "given": "Sari", "initials": "S"}, {"family": "Branca", "given": "Rui M M", "initials": "RMM"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J"}, {"family": "Cerullo", "given": "Vincenzo", "initials": "V", "orcid": "0000-0003-4901-3796", "researcher": {"href": "https://publications.scilifelab.se/researcher/6404cf54a990420fb0b63d626aa783fb.json"}}], "type": "journal article", "published": "2021-07-07", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "13", "issue": "14", "issn-l": "2072-6694"}, "abstract": "Knowledge of clinically targetable tumor antigens is becoming vital for broader design and utility of therapeutic cancer vaccines. This information is obtained reliably by directly interrogating the MHC-I presented peptide ligands, the immunopeptidome, with state-of-the-art mass spectrometry. Our manuscript describes direct identification of novel tumor antigens for an aggressive triple-negative breast cancer model. Immunopeptidome profiling revealed 2481 unique antigens, among them a novel ERV antigen originating from an endogenous retrovirus element. The clinical benefit and tumor control potential of the identified tumor antigens and ERV antigen were studied in a preclinical model using two vaccine platforms and therapeutic settings. Prominent control of established tumors was achieved using an oncolytic adenovirus platform designed for flexible and specific tumor targeting, namely PeptiCRAd. Our study presents a pipeline integrating immunopeptidome analysis-driven antigen discovery with a therapeutic cancer vaccine platform for improved personalized oncolytic immunotherapy.", "doi": "10.3390/cancers13143408", "pmid": "34298622", "labels": {"Global Proteomics and Proteogenomics": "Technology development"}, "xrefs": [{"db": "pii", "key": "cancers13143408"}, {"db": "pmc", "key": "PMC8306067"}], "notes": [], "created": "2021-12-10T07:03:05.402Z", "modified": "2021-12-10T07:03:05.579Z"}, {"entity": "publication", "iuid": "394b989e896342f8a803356dbb5e5c2f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/394b989e896342f8a803356dbb5e5c2f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/394b989e896342f8a803356dbb5e5c2f"}}, "title": "Proteomic Profiling of Tissue Exosomes Indicates Continuous Release of Malignant Exosomes in Urinary Bladder Cancer Patients, Even with Pathologically Undetectable Tumour.", "authors": [{"family": "Eldh", "given": "Maria", "initials": "M"}, {"family": "Mints", "given": "Michael", "initials": "M"}, {"family": "Hiltbrunner", "given": "Stefanie", "initials": "S", "orcid": "0000-0002-3415-7992", "researcher": {"href": "https://publications.scilifelab.se/researcher/b80636a6106f48d5892e99e58249412e.json"}}, {"family": "Ladjevardi", "given": "Sam", "initials": "S"}, {"family": "Alamdari", "given": "Farhood", "initials": "F"}, {"family": "Johansson", "given": "Markus", "initials": "M"}, {"family": "Jakubczyk", "given": "Tomasz", "initials": "T"}, {"family": "Veerman", "given": "Rosanne E", "initials": "RE"}, {"family": "Winqvist", "given": "Ola", "initials": "O"}, {"family": "Sherif", "given": "Amir", "initials": "A", "orcid": "0000-0002-3675-3050", "researcher": {"href": "https://publications.scilifelab.se/researcher/e27ad5d3def147849d4821d86075c3d2.json"}}, {"family": "Gabrielsson", "given": "Susanne", "initials": "S", "orcid": "0000-0003-1771-1346", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d446cb52d7e4a01ad8478a9cfe22ae1.json"}}], "type": "journal article", "published": "2021-06-29", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "13", "issue": "13", "issn-l": "2072-6694"}, "abstract": "Invasive urothelial bladder cancer (UBC) has high recurrence rates even after radical cystectomy (RC). Exosomes are membrane-bound nanovesicles, which have been shown to contribute to carcinogenesis and metastasis. We previously showed that urinary exosomes display a malignant profile in UBC patients despite the absence of detectable tumour. Here, we investigated exosomes from sampling sites close to or distant from the former tumour, aiming to understand the effect of the tumour on the local milieu. Ten patients scheduled for cystectomy after transurethral bladder resection (TUR-B), without remaining detectable tumour, were included. Exosomes were isolated from tissue explants of both the previous tumour site and distant bladder tissue. Proteins were quantified by mass spectrometry in seven patients. Exosomes from the previous tumour site were enriched in inflammatory but not cancer-related pathways compared to distant tissue. However, the 69 most abundant proteins in tissue-derived exosomes regardless of site, 20 of which were also found in urinary exosomes from our previous study, were enriched for cancer-related metabolic pathways and associated with poor prognosis in an external mRNA dataset. The enrichment of cancer-related pathways in the most abundant proteins, regardless of sampling site, confirms our hypothesis that despite the absence of detectable tumour, the entire bladder releases exosomes that contribute to metastasis and highlights the need for early RC.", "doi": "10.3390/cancers13133242", "pmid": "34209558", "labels": {"Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "cancers13133242"}, {"db": "pmc", "key": "PMC8267924"}], "notes": [], "created": "2022-03-29T12:09:27.244Z", "modified": "2022-03-29T12:09:27.355Z"}, {"entity": "publication", "iuid": "37a57995a5b84f1da07545fd29e58163", "links": {"self": {"href": "https://publications.scilifelab.se/publication/37a57995a5b84f1da07545fd29e58163.json"}, "display": {"href": "https://publications.scilifelab.se/publication/37a57995a5b84f1da07545fd29e58163"}}, "title": "Identification of Candidate Protein Biomarkers for CIN2+ Lesions from Self-Sampled, Dried Cervico-Vaginal Fluid Using LC-MS/MS.", "authors": [{"family": "Guti\u00e9rrez", "given": "Ariadna Lara", "initials": "AL", "orcid": "0000-0003-3584-0627", "researcher": {"href": "https://publications.scilifelab.se/researcher/76b18f907c414f258383f9fde9798a75.json"}}, {"family": "Lindberg", "given": "Julia Hedlund", "initials": "JH"}, {"family": "Shevchenko", "given": "Ganna", "initials": "G"}, {"family": "Gustavsson", "given": "Inger", "initials": "I"}, {"family": "Bergquist", "given": "Jonas", "initials": "J", "orcid": "0000-0002-4597-041X", "researcher": {"href": "https://publications.scilifelab.se/researcher/d745034529f3423abbea230b4e586d20.json"}}, {"family": "Gyllensten", "given": "Ulf", "initials": "U"}, {"family": "Enroth", "given": "Stefan", "initials": "S", "orcid": "0000-0002-5056-9137", "researcher": {"href": "https://publications.scilifelab.se/researcher/16bb97ef16ee49f3ae0c7ea0495fd971.json"}}], "type": "journal article", "published": "2021-05-25", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "13", "issue": "11", "issn-l": "2072-6694"}, "abstract": "Molecular screening programs for cervical cancer detect the presence of human papilloma virus (HPV) in cell material or vaginal fluids. Persistent infection with high-risk HPV is a necessary pre-requisite, but the majority of infections do not lead to pathological states. Additional biomarkers are needed to increase the specificity of the molecular tests. Here, we have investigated the possibility of detecting protein biomarkers using mass spectrometry from dried self-sampled cervico-vaginal fluid deposited on FTA cards. We found significant intra-individual correlations (p < 2.2 \u00d7 10-16), although heterogenous protein profiles were obtained between individuals. Out of 3699 proteins found in total, 169 were detected in at least 95% of the samples. Using a discovery/replication design, 18 proteins were found to be significant in the discovery cohort, with higher values in those cases compared to controls. All of these were found to also have higher levels among the cases in the replication cohort, with one protein (DEAD-Box Helicase) remaining statistically significant. Finally, a predictive 7-protein multivariate model was developed with a sensitivity and specificity of 0.90 and 0.55, respectively. Our results demonstrate that robust measurements of protein biomarkers can be obtained from self-sampled dried CVF and that these could be used to predict cervical cancer pre-stages.", "doi": "10.3390/cancers13112592", "pmid": "34070587", "labels": {"Bioinformatics (NBIS)": "Service", "Bioinformatics Support and Infrastructure": "Service", "Bioinformatics Support, Infrastructure and Training": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8198222"}, {"db": "pii", "key": "cancers13112592"}], "notes": [], "created": "2025-11-21T13:13:36.269Z", "modified": "2025-11-21T13:13:36.473Z"}, {"entity": "publication", "iuid": "757c0e21579245efa977aa225a84d8f6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/757c0e21579245efa977aa225a84d8f6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/757c0e21579245efa977aa225a84d8f6"}}, "title": "Loss of RET Promotes Mesenchymal Identity in Neuroblastoma Cells.", "authors": [{"family": "Siaw", "given": "Joachim T", "initials": "JT"}, {"family": "Gabre", "given": "Jonatan L", "initials": "JL", "orcid": "0000-0001-6278-7556", "researcher": {"href": "https://publications.scilifelab.se/researcher/db6ad399868d45ac9610b627a063c57a.json"}}, {"family": "U\u00e7kun", "given": "Ezgi", "initials": "E", "orcid": "0000-0002-7745-8277", "researcher": {"href": "https://publications.scilifelab.se/researcher/d860e37cd83d41fe9aa44c13fc063559.json"}}, {"family": "Vigny", "given": "Marc", "initials": "M"}, {"family": "Zhang", "given": "Wancun", "initials": "W"}, {"family": "Van den Eynden", "given": "Jimmy", "initials": "J", "orcid": "0000-0003-0002-5614", "researcher": {"href": "https://publications.scilifelab.se/researcher/8b20f02703024987bc9791df1dc80e51.json"}}, {"family": "Hallberg", "given": "Bengt", "initials": "B", "orcid": "0000-0003-2032-2616", "researcher": {"href": "https://publications.scilifelab.se/researcher/e34241a23a824d558865ac54d8d07fa7.json"}}, {"family": "Palmer", "given": "Ruth H", "initials": "RH", "orcid": "0000-0002-2735-8470", "researcher": {"href": "https://publications.scilifelab.se/researcher/808281ecc2634b66a274895e58a122bd.json"}}, {"family": "Guan", "given": "Jikui", "initials": "J", "orcid": "0000-0003-1723-0307", "researcher": {"href": "https://publications.scilifelab.se/researcher/a39044157aa7475485fb489a003b63d1.json"}}], "type": "journal article", "published": "2021-04-15", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "13", "issue": "8", "issn-l": "2072-6694"}, "abstract": "Aberrant activation of anaplastic lymphoma kinase (ALK) drives neuroblastoma (NB). Previous work identified the RET receptor tyrosine kinase (RTK) as a downstream target of ALK activity in NB models. We show here that ALK activation in response to ALKAL2 ligand results in the rapid phosphorylation of RET in NB cells, providing additional insight into the contribution of RET to the ALK-driven gene signature in NB. To further address the role of RET in NB, RET knockout (KO) SK-N-AS cells were generated by CRISPR/Cas9 genome engineering. Gene expression analysis of RET KO NB cells identified a reprogramming of NB cells to a mesenchymal (MES) phenotype that was characterized by increased migration and upregulation of the AXL and MNNG HOS transforming gene (MET) RTKs, as well as integrins and extracellular matrix components. Strikingly, the upregulation of AXL in the absence of RET reflects the development timeline observed in the neural crest as progenitor cells undergo differentiation during embryonic development. Together, these findings suggest that a MES phenotype is promoted in mesenchymal NB cells in the absence of RET, reflective of a less differentiated developmental status.", "doi": "10.3390/cancers13081909", "pmid": "33921066", "labels": {"Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8071449"}, {"db": "pii", "key": "cancers13081909"}], "notes": [], "created": "2023-03-07T14:36:38.630Z", "modified": "2024-01-16T13:46:30.696Z"}, {"entity": "publication", "iuid": "d5a79a3f31dc4f9abe7b168539cb06ea", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d5a79a3f31dc4f9abe7b168539cb06ea.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d5a79a3f31dc4f9abe7b168539cb06ea"}}, "title": "Deletions on Chromosome Y and Downregulation of the SRY Gene in Tumor Tissue Are Associated with Worse Survival of Glioblastoma Patients.", "authors": [{"family": "\u0141ysiak", "given": "Ma\u0142gorzata", "initials": "M", "orcid": "0000-0002-0244-759X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7f5d37e79764c31a5a0a421c34ed1a8.json"}}, {"family": "Smits", "given": "Anja", "initials": "A", "orcid": "0000-0003-4171-2672", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e73b52dac6b4262a1aef442afe4a1f7.json"}}, {"family": "Roodakker", "given": "Kenney Roy", "initials": "KR"}, {"family": "Sandberg", "given": "Elisabeth", "initials": "E", "orcid": "0000-0002-9230-4751", "researcher": {"href": "https://publications.scilifelab.se/researcher/997fb5a248df416d99543a2c7a8e019a.json"}}, {"family": "Dimberg", "given": "Anna", "initials": "A"}, {"family": "Mudaisi", "given": "Munila", "initials": "M"}, {"family": "Bratth\u00e4ll", "given": "Charlotte", "initials": "C"}, {"family": "Strandeus", "given": "Michael", "initials": "M"}, {"family": "Milos", "given": "Peter", "initials": "P"}, {"family": "Hallbeck", "given": "Martin", "initials": "M"}, {"family": "S\u00f6derkvist", "given": "Peter", "initials": "P"}, {"family": "Malmstr\u00f6m", "given": "Annika", "initials": "A", "orcid": "0000-0001-8410-4939", "researcher": {"href": "https://publications.scilifelab.se/researcher/34a15d92ca7442dcaec76288815f724c.json"}}], "type": "journal article", "published": "2021-03-31", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "issn-l": "2072-6694", "volume": "13", "issue": "7", "pages": null}, "abstract": "Biological causes of sex disparity seen in the prevalence of cancer, including glioblastoma (GBM), remain poorly understood. One of the considered aspects is the involvement of the sex chromosomes, especially loss of chromosome Y (LOY).\r\n\r\nTumors from 105 isocitrate dehydrogenase (IDH) wild type male GBM patients were tested with droplet digital PCR for copy number changes of ten genes on chromosome Y. Decreased gene expression, a proxy of gene loss, was then analyzed in 225 IDH wild type GBM derived from TCGA and overall survival in both cohorts was tested with Kaplan-Meier log-rank analysis and maximally selected rank statistics for cut-off determination.\r\n\r\nLOY was associated with significantly shorter overall survival (7 vs. 14.6 months, p = 0.0016), and among investigated individual genes survival correlated most prominently with loss of the sex-determining region Y gene (SRY) (10.8 vs. 14.8 months, p = 0.0031). Gene set enrichment analysis revealed that epidermal growth factor receptor, platelet-derived growth factor receptor, and MYC proto-oncogene signaling pathways are associated with low SRY expression.\r\n\r\nOur data show that deletions and reduced gene expression of chromosome Y genes, especially SRY, are associated with reduced survival of male GBM patients and connected to major susceptibility pathways of gliomagenesis.", "doi": "10.3390/cancers13071619", "pmid": "33807423", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "cancers13071619"}, {"db": "pmc", "key": "PMC8036637"}], "notes": [], "created": "2021-12-09T13:01:58.155Z", "modified": "2021-12-09T13:02:14.872Z"}, {"entity": "publication", "iuid": "a6c74c26d13a4608b4806234c6d580d5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a6c74c26d13a4608b4806234c6d580d5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a6c74c26d13a4608b4806234c6d580d5"}}, "title": "Identification of Pre-Diagnostic Metabolic Patterns for Glioma Using Subset Analysis of Matched Repeated Time Points.", "authors": [{"family": "Jonsson", "given": "P\u00e4r", "initials": "P", "orcid": "0000-0001-8357-5018", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd630ff903db4a61af5bf65a46c9c098.json"}}, {"family": "Antti", "given": "Henrik", "initials": "H"}, {"family": "Sp\u00e4th", "given": "Florentin", "initials": "F"}, {"family": "Melin", "given": "Beatrice", "initials": "B"}, {"family": "Bj\u00f6rkblom", "given": "Benny", "initials": "B", "orcid": "0000-0001-9347-5790", "researcher": {"href": "https://publications.scilifelab.se/researcher/acf29b039dfc496fb33c0cf7cb1d587c.json"}}], "type": "journal article", "published": "2020-11-12", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "12", "issue": "11", "pages": "3349", "issn-l": "2072-6694"}, "abstract": "Here, we present a strategy for early molecular marker pattern detection-Subset analysis of Matched Repeated Time points (SMART)-used in a mass-spectrometry-based metabolomics study of repeated blood samples from future glioma patients and their matched controls. The outcome from SMART is a predictive time span when disease-related changes are detectable, defined by time to diagnosis and time between longitudinal sampling, and visualization of molecular marker patterns related to future disease. For glioma, we detect significant changes in metabolite levels as early as eight years before diagnosis, with longitudinal follow up within seven years. Elevated blood plasma levels of myo-inositol, cysteine, N-acetylglucosamine, creatinine, glycine, proline, erythronic-, 4-hydroxyphenylacetic-, uric-, and aceturic acid were particularly evident in glioma cases. We use data simulation to ensure non-random events and a separate data set for biomarker validation. The latent biomarker, consisting of 15 interlinked and significantly altered metabolites, shows a strong correlation to oxidative metabolism, glutathione biosynthesis and monosaccharide metabolism, linked to known early events in tumor development. This study highlights the benefits of progression pattern analysis and provide a tool for the discovery of early markers of disease.", "doi": "10.3390/cancers12113349", "pmid": "33198241", "labels": {"Bioinformatics Support for Computational Resources": "Service", "Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pii", "key": "cancers12113349"}, {"db": "pmc", "key": "PMC7696703"}], "notes": [], "created": "2020-12-11T12:04:50.936Z", "modified": "2025-10-17T13:03:16.601Z"}, {"entity": "publication", "iuid": "d35dda9e1c1e4f48ae002543b503d001", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d35dda9e1c1e4f48ae002543b503d001.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d35dda9e1c1e4f48ae002543b503d001"}}, "title": "Ex Vivo Organoid Cultures Reveal the Importance of the Tumor Microenvironment for Maintenance of Colorectal Cancer Stem Cells.", "authors": [{"family": "Li", "given": "Xingru", "initials": "X"}, {"family": "Larsson", "given": "P\u00e4r", "initials": "P", "orcid": "0000-0001-9054-5191", "researcher": {"href": "https://publications.scilifelab.se/researcher/573c6350305a49cba2ac0798dea21ae0.json"}}, {"family": "Ljuslinder", "given": "Ingrid", "initials": "I"}, {"family": "\u00d6hlund", "given": "Daniel", "initials": "D", "orcid": "0000-0002-5847-2778", "researcher": {"href": "https://publications.scilifelab.se/researcher/42e9e473f68c460098a37e22d0a41369.json"}}, {"family": "Myte", "given": "Robin", "initials": "R"}, {"family": "L\u00f6fgren-Burstr\u00f6m", "given": "Anna", "initials": "A"}, {"family": "Zingmark", "given": "Carl", "initials": "C"}, {"family": "Ling", "given": "Agnes", "initials": "A"}, {"family": "Edin", "given": "Sofia", "initials": "S"}, {"family": "Palmqvist", "given": "Richard", "initials": "R", "orcid": "0000-0002-9933-2843", "researcher": {"href": "https://publications.scilifelab.se/researcher/40ae823e5364458b8f957a65a82c741f.json"}}], "type": "journal article", "published": "2020-04-10", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "issn-l": "2072-6694", "volume": "12", "issue": "4", "pages": "923"}, "abstract": "Colorectal cancer (CRC) is a heterogeneous disease, with varying clinical presentations and patient prognosis. Different molecular subgroups of CRC should be treated differently and therefore, must be better characterized. Organoid culture has recently been suggested as a good model to reflect the heterogeneous nature of CRC. However, organoid cultures cannot be established from all CRC tumors. The study examines which CRC tumors are more likely to generate organoids and thus benefit from ex vivo organoid drug testing. Long-term organoid cultures from 22 out of 40 CRC tumor specimens were established. It was found that organoid cultures were more difficult to establish from tumors characterized as microsatellite instable (MSI), BRAF-mutated, poorly differentiated and/or of a mucinous type. This suggests that patients with such tumors are less likely to benefit from ex vivo organoid drug testing, but it may also suggest biological difference in tumor growth. RNA sequencing analysis of tumor sections revealed that the in vivo maintenance of these non-organoid-forming tumors depends on factors related to inflammation and pathogen exposure. Furthermore, using TCGA data we could show a trend towards a worse prognosis for patients with organoid-forming tumors, suggesting also clinical differences. Results suggest that organoids are more difficult to establish from tumors characterized as MSI, BRAF-mutated, poorly differentiated and/or of a mucinous type. We further suggest that the maintenance of cell growth of these tumors in vivo may be promoted by immune-related factors and other stromal components within the tumor microenvironment.", "doi": "10.3390/cancers12040923", "pmid": "32290033", "labels": {"Clinical Genomics Ume\u00e5": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "cancers12040923"}, {"db": "pmc", "key": "PMC7226030"}], "notes": [], "created": "2021-06-18T11:54:38.900Z", "modified": "2021-12-08T14:16:21.865Z"}, {"entity": "publication", "iuid": "a074964a79c24ad1b92ce498859976e4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a074964a79c24ad1b92ce498859976e4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a074964a79c24ad1b92ce498859976e4"}}, "title": "Molecular Profiling for Predictors of Radiosensitivity in Patients with Breast or Head-and-Neck Cancer.", "authors": [{"family": "Drobin", "given": "Kimi", "initials": "K"}, {"family": "Marczyk", "given": "Michal", "initials": "M", "orcid": "0000-0003-2508-5736", "researcher": {"href": "https://publications.scilifelab.se/researcher/f41817907c56448991e2c9e94f15da42.json"}}, {"family": "Halle", "given": "Martin", "initials": "M"}, {"family": "Danielsson", "given": "Daniel", "initials": "D", "orcid": "0000-0001-9407-2774", "researcher": {"href": "https://publications.scilifelab.se/researcher/45064e20ddfc4eadb626612584d8f95a.json"}}, {"family": "Papiez", "given": "Anna", "initials": "A", "orcid": "0000-0003-0179-1302", "researcher": {"href": "https://publications.scilifelab.se/researcher/f12e4932eb264f0096db641d0915e3b6.json"}}, {"family": "Sangsuwan", "given": "Traimate", "initials": "T", "orcid": "0000-0003-4051-8376", "researcher": {"href": "https://publications.scilifelab.se/researcher/7521353e59bd45f68393e2f85b2a978f.json"}}, {"family": "Bendes", "given": "Annika", "initials": "A", "orcid": "0000-0001-9329-2353", "researcher": {"href": "https://publications.scilifelab.se/researcher/50dffce4f4444dd8b5ff8f9294146a0b.json"}}, {"family": "Hong", "given": "Mun-Gwan", "initials": "MG", "orcid": "0000-0001-8603-8293", "researcher": {"href": "https://publications.scilifelab.se/researcher/5d66c199ece143a6ab15222d8b55e3ea.json"}}, {"family": "Qundos", "given": "Ulrika", "initials": "U"}, {"family": "Harms-Ringdahl", "given": "Mats", "initials": "M"}, {"family": "Wers\u00e4ll", "given": "Peter", "initials": "P"}, {"family": "Polanska", "given": "Joanna", "initials": "J", "orcid": "0000-0001-8004-9864", "researcher": {"href": "https://publications.scilifelab.se/researcher/329d4bcbf1e64ecca6bc2b3505cc8901.json"}}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM", "orcid": "0000-0001-8141-8449", "researcher": {"href": "https://publications.scilifelab.se/researcher/aba5822711b246b397fffacb7ae403b3.json"}}, {"family": "Haghdoost", "given": "Siamak", "initials": "S", "orcid": "0000-0002-2867-4774", "researcher": {"href": "https://publications.scilifelab.se/researcher/e53acb351cb34d49924b840e1b2d2dc1.json"}}], "type": "journal article", "published": "2020-03-22", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "issn-l": "2072-6694", "volume": "12", "issue": "3", "pages": "753"}, "abstract": "Nearly half of all cancers are treated with radiotherapy alone or in combination with other treatments, where damage to normal tissues is a limiting factor for the treatment. Radiotherapy-induced adverse health effects, mostly of importance for cancer patients with long-term survival, may appear during or long time after finishing radiotherapy and depend on the patient's radiosensitivity. Currently, there is no assay available that can reliably predict the individual's response to radiotherapy. We profiled two study sets from breast (n = 29) and head-and-neck cancer patients (n = 74) that included radiosensitive patients and matched radioresistant controls.. We studied 55 single nucleotide polymorphisms (SNPs) in 33 genes by DNA genotyping and 130 circulating proteins by affinity-based plasma proteomics. In both study sets, we discovered several plasma proteins with the predictive power to find radiosensitive patients (adjusted p < 0.05) and validated the two most predictive proteins (THPO and STIM1) by sandwich immunoassays. By integrating genotypic and proteomic data into an analysis model, it was found that the proteins CHIT1, PDGFB, PNKD, RP2, SERPINC1, SLC4A, STIM1, and THPO, as well as the VEGFA gene variant rs69947, predicted radiosensitivity of our breast cancer (AUC = 0.76) and head-and-neck cancer (AUC = 0.89) patients. In conclusion, circulating proteins and a SNP variant of VEGFA suggest that processes such as vascular growth capacity, immune response, DNA repair and oxidative stress/hypoxia may be involved in an individual's risk of experiencing radiation-induced toxicity.", "doi": "10.3390/cancers12030753", "pmid": "32235817", "labels": {"Affinity Proteomics Stockholm": "Collaborative"}, "xrefs": [{"db": "pii", "key": "cancers12030753"}, {"db": "pmc", "key": "PMC7140105"}], "notes": [], "created": "2020-12-10T19:03:40.959Z", "modified": "2021-11-10T12:52:54.485Z"}, {"entity": "publication", "iuid": "edac35c02fd041b1b4e22d060da8ff14", "links": {"self": {"href": "https://publications.scilifelab.se/publication/edac35c02fd041b1b4e22d060da8ff14.json"}, "display": {"href": "https://publications.scilifelab.se/publication/edac35c02fd041b1b4e22d060da8ff14"}}, "title": "Gene Expression Alterations during Development of Castration-Resistant Prostate Cancer Are Detected in Circulating Tumor Cells.", "authors": [{"family": "Josefsson", "given": "Andreas", "initials": "A"}, {"family": "Larsson", "given": "Karin", "initials": "K"}, {"family": "Freyhult", "given": "Eva", "initials": "E"}, {"family": "Damber", "given": "Jan-Erik", "initials": "J"}, {"family": "Wel\u00e9n", "given": "Karin", "initials": "K"}], "type": "journal article", "published": "2019-12-21", "journal": {"volume": "12", "issn": "2072-6694", "issue": "1", "pages": null, "title": "Cancers (Basel)", "issn-l": "2072-6694"}, "abstract": "Development of castration-resistant prostate cancer (CRPC) is associated with alterations in gene expression involved in steroidogenesis and androgen signaling. This study investigates whether gene expression changes related to CRPC development can be identified in circulating tumor cells (CTCs). Gene expression in paired CTC samples from 29 patients, before androgen deprivation therapy (ADT) and at CRPC relapse, was compared using a panel including 47 genes related to prostate cancer progression on a qPCR platform. Fourteen genes displayed significantly changed gene expression in CTCs at CRPC relapse compared to before start of ADT. The genes with increased expression at CRPC relapse were related to steroidogenesis, AR-signaling, and anti-apoptosis. In contrast, expression of prostate markers was downregulated at CRPC. We also show that midkine (MDK) expression in CTCs from metastatic hormone-sensitive prostate cancer (mHSPC) was associated to short cancer-specific survival (CSS). In conclusion, this study shows that gene expression patterns in CTCs reflect the development of CRPC, and that MDK expression levels in CTCs are prognostic for cancer-specific survival in mHSPC. This study emphasizes the role of CTCs in exploring mechanisms of therapy resistance, as well as a promising biomarker for prognostic and treatment-predictive purposes in advanced mHSPC.", "doi": "10.3390/cancers12010039", "pmid": "31877738", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "cancers12010039"}], "notes": [], "created": "2020-01-07T08:53:35.031Z", "modified": "2020-12-10T16:19:41.750Z"}, {"entity": "publication", "iuid": "adfd8ccfb65c4f3e84f2dd566e88d0ad", "links": {"self": {"href": "https://publications.scilifelab.se/publication/adfd8ccfb65c4f3e84f2dd566e88d0ad.json"}, "display": {"href": "https://publications.scilifelab.se/publication/adfd8ccfb65c4f3e84f2dd566e88d0ad"}}, "title": "The Hidden Story of Heterogeneous B-raf V600E Mutation Quantitative Protein Expression in Metastatic Melanoma-Association with Clinical Outcome and Tumor Phenotypes.", "authors": [{"family": "Betancourt", "given": "Lazaro Hiram", "initials": "LH"}, {"family": "Szasz", "given": "A Marcell", "initials": "AM"}, {"family": "Kuras", "given": "Magdalena", "initials": "M"}, {"family": "Rodriguez Murillo", "given": "Jimmy", "initials": "J"}, {"family": "Sugihara", "given": "Yutaka", "initials": "Y"}, {"family": "Pla", "given": "Indira", "initials": "I"}, {"family": "Horvath", "given": "Zsolt", "initials": "Z"}, {"family": "Paw\u0142owski", "given": "Krzysztof", "initials": "K"}, {"family": "Rezeli", "given": "Melinda", "initials": "M"}, {"family": "Miharada", "given": "Kenichi", "initials": "K"}, {"family": "Gil", "given": "Jeovanis", "initials": "J"}, {"family": "Eriksson", "given": "Jonatan", "initials": "J"}, {"family": "Appelqvist", "given": "Roger", "initials": "R"}, {"family": "Miliotis", "given": "Tasso", "initials": "T"}, {"family": "Baldetorp", "given": "Bo", "initials": "B"}, {"family": "Ingvar", "given": "Christian", "initials": "C"}, {"family": "Olsson", "given": "H\u00e5kan", "initials": "H"}, {"family": "Lundgren", "given": "Lotta", "initials": "L"}, {"family": "Horvatovich", "given": "Peter", "initials": "P"}, {"family": "Welinder", "given": "Charlotte", "initials": "C"}, {"family": "Wieslander", "given": "Elisabet", "initials": "E"}, {"family": "Kwon", "given": "Ho Jeong", "initials": "HJ"}, {"family": "Malm", "given": "Johan", "initials": "J"}, {"family": "Nemeth", "given": "Istvan Balazs", "initials": "IB"}, {"family": "J\u00f6nsson", "given": "G\u00f6ran", "initials": "G"}, {"family": "Feny\u00f6", "given": "David", "initials": "D"}, {"family": "Sanchez", "given": "Aniel", "initials": "A"}, {"family": "Marko-Varga", "given": "Gy\u00f6rgy", "initials": "G"}], "type": "journal article", "published": "2019-12-09", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "11", "issue": "12", "issn-l": "2072-6694"}, "abstract": "In comparison to other human cancer types, malignant melanoma exhibits the greatest amount of heterogeneity. After DNA-based detection of the BRAF V600E mutation in melanoma patients, targeted inhibitor treatment is the current recommendation. This approach, however, does not take the abundance of the therapeutic target, i.e., the B-raf V600E protein, into consideration. As shown by immunohistochemistry, the protein expression profiles of metastatic melanomas clearly reveal the existence of inter- and intra-tumor variability. Nevertheless, the technique is only semi-quantitative. To quantitate the mutant protein there is a fundamental need for more precise techniques that are aimed at defining the currently non-existent link between the levels of the target protein and subsequent drug efficacy. Using cutting-edge mass spectrometry combined with DNA and mRNA sequencing, the mutated B-raf protein within metastatic tumors was quantitated for the first time. B-raf V600E protein analysis revealed a subjacent layer of heterogeneity for mutation-positive metastatic melanomas. These were characterized into two distinct groups with different tumor morphologies, protein profiles and patient clinical outcomes. This study provides evidence that a higher level of expression in the mutated protein is associated with a more aggressive tumor progression. Our study design, comprised of surgical isolation of tumors, histopathological characterization, tissue biobanking, and protein analysis, may enable the eventual delineation of patient responders/non-responders and subsequent therapy for malignant melanoma.", "doi": "10.3390/cancers11121981", "pmid": "31835364", "labels": {"Structural Proteomics": "Service"}, "xrefs": [{"db": "pii", "key": "cancers11121981"}], "notes": [], "created": "2020-01-27T10:08:48.170Z", "modified": "2021-05-24T15:39:50.361Z"}, {"entity": "publication", "iuid": "be135146fd7c406a88c1ff9664b6e423", "links": {"self": {"href": "https://publications.scilifelab.se/publication/be135146fd7c406a88c1ff9664b6e423.json"}, "display": {"href": "https://publications.scilifelab.se/publication/be135146fd7c406a88c1ff9664b6e423"}}, "title": "GLUL Ablation Can Confer Drug Resistance to Cancer Cells via a Malate-Aspartate Shuttle-Mediated Mechanism.", "authors": [{"family": "Muthu", "given": "Magesh", "initials": "M"}, {"family": "Kumar", "given": "Ranjeet", "initials": "R"}, {"family": "Syed Khaja", "given": "Azharuddin Sajid", "initials": "AS", "orcid": "0000-0003-1594-1826", "researcher": {"href": "https://publications.scilifelab.se/researcher/aa3cc7ab186b447987513bbad0ab7d92.json"}}, {"family": "Gilthorpe", "given": "Jonathan D", "initials": "JD", "orcid": "0000-0002-6884-4774", "researcher": {"href": "https://publications.scilifelab.se/researcher/7eb2a4f38fdc4e0db2516a17d9abdf06.json"}}, {"family": "Persson", "given": "Jenny L", "initials": "JL"}, {"family": "Nordstr\u00f6m", "given": "Anders", "initials": "A", "orcid": "0000-0003-3676-817X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4b1803a3f7624f0d82abd552448bdaed.json"}}], "type": "journal article", "published": "2019-12-05", "journal": {"volume": "11", "issn": "2072-6694", "issue": "12", "pages": "1945", "title": "Cancers (Basel)", "issn-l": "2072-6694"}, "abstract": "Glutamate-ammonia ligase (GLUL) is important for acid-base homeostasis, ammonia detoxification, cell signaling, and proliferation. Here, we reported that GLUL ablation conferred resistance to several anticancer drugs in specific cancer cell lines while leaving other cell lines non-resistant to the same drugs. To understand the biochemical mechanics supporting this drug resistance, we compared drug-resistant GLUL knockout (KO) A549 non-small-cell lung carcinoma (NSCLC) cells with non-resistant GLUL KO H1299 NSCLC cells and found that the resistant A549 cells, to a larger extent, depended on exogenous glucose for proliferation. As GLUL activity is linked to the tricarboxylic acid (TCA) cycle via reversed glutaminolysis, we probed carbon flux through both glycolysis and TCA pathways by means of 13C5 glutamine, 13C5 glutamate, and 13C6 glucose tracing. We observed increased labeling of malate and aspartate in A549 GLUL KO cells, whereas the non-resistant GLUL KO H1299 cells displayed decreased 13C-labeling. The malate and aspartate shuttle supported cellular NADH production and was associated with cellular metabolic fitness. Inhibition of the malate-aspartate shuttle with aminooxyacetic acid significantly impacted upon cell viability with an IC50 of 11.5 \u03bcM in resistant GLUL KO A549 cells compared to 28 \u03bcM in control A549 cells, linking resistance to the malate-aspartate shuttle. Additionally, rescuing GLUL expression in A549 KO cells increased drug sensitivity. We proposed a novel metabolic mechanism in cancer drug resistance where the increased capacity of the malate-aspartate shuttle increased metabolic fitness, thereby facilitating cancer cells to escape drug pressure.", "doi": "10.3390/cancers11121945", "pmid": "31817360", "labels": {"Bioinformatics Support for Computational Resources": "Service", "Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pii", "key": "cancers11121945"}, {"db": "pmc", "key": "PMC6966511"}], "notes": [], "created": "2020-01-07T15:45:49.261Z", "modified": "2025-10-17T13:03:17.024Z"}], "created": "2020-01-07T08:53:35.038Z", "modified": "2020-11-27T13:14:09.052Z"}