{"entity": "journal", "iuid": "1cfa24dfe6b64535b3290bdee9e6a8b3", "timestamp": "2026-08-15T12:40:20.441Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Int.%20J.%20Cancer.json"}, "display": {"href": "https://publications.scilifelab.se/journal/Int.%20J.%20Cancer"}}, "title": "Int. J. Cancer", "issn": "1097-0215", "issn-l": "0020-7136", "publications_count": 17, "publications": [{"entity": "publication", "iuid": "60d83cc8c444462f8cfce90048ed5781", "links": {"self": {"href": "https://publications.scilifelab.se/publication/60d83cc8c444462f8cfce90048ed5781.json"}, "display": {"href": "https://publications.scilifelab.se/publication/60d83cc8c444462f8cfce90048ed5781"}}, "title": "Clinical and genetic factors associated with tumor response to neoadjuvant (chemo)radiotherapy, survival and recurrence risk in rectal cancer.", "authors": [{"family": "Hammarstr\u00f6m", "given": "Klara", "initials": "K", "orcid": "0000-0002-8271-2241", "researcher": {"href": "https://publications.scilifelab.se/researcher/8e06b1abd3594e3db5eb216271b0b0a4.json"}}, {"family": "Nunes", "given": "Lu\u00eds", "initials": "L", "orcid": "0000-0002-3391-1607", "researcher": {"href": "https://publications.scilifelab.se/researcher/9be3293494cd4efe9bab07504cc1fcd0.json"}}, {"family": "Mathot", "given": "Lucy", "initials": "L", "orcid": "0000-0002-2990-2038", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9f3bfe35ddf41e5beb4312d3408a7ea.json"}}, {"family": "Mezheyeuski", "given": "Artur", "initials": "A", "orcid": "0000-0002-4394-2634", "researcher": {"href": "https://publications.scilifelab.se/researcher/dd907ed1df0441b99789d3e045c4d890.json"}}, {"family": "Lundin", "given": "Emma", "initials": "E", "orcid": "0009-0000-7711-1962", "researcher": {"href": "https://publications.scilifelab.se/researcher/06761839da88443e9098d9562810fb7f.json"}}, {"family": "Korsavidou Hult", "given": "Nafsika", "initials": "N", "orcid": "0000-0002-5562-449X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eeafca618c14d40b4bd78b4a08f3774.json"}}, {"family": "Imam", "given": "Israa", "initials": "I", "orcid": "0000-0002-0232-2391", "researcher": {"href": "https://publications.scilifelab.se/researcher/15735120d46649e6ba5cd94c925fd375.json"}}, {"family": "Osterlund", "given": "Emerik", "initials": "E", "orcid": "0000-0003-0973-6332", "researcher": {"href": "https://publications.scilifelab.se/researcher/edf1c930ec4149e59a952cd04ff0a4f8.json"}}, {"family": "Sj\u00f6blom", "given": "Tobias", "initials": "T", "orcid": "0000-0001-6668-4140", "researcher": {"href": "https://publications.scilifelab.se/researcher/909f00a5bf6e465f9ff560b12bcd863a.json"}}, {"family": "Glimelius", "given": "Bengt", "initials": "B", "orcid": "0000-0002-5440-791X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e79e661083f49bf90cbbfc19670f404.json"}}], "type": "journal article", "published": "2024-07-01", "journal": {"title": "Int. J. Cancer", "issn": "1097-0215", "volume": "155", "issue": "1", "pages": "40-53", "issn-l": "0020-7136"}, "abstract": "Rectal cancer poses challenges in preoperative treatment response, with up to 30% achieving a complete response (CR). Personalized treatment relies on accurate identification of responders at diagnosis. This study aimed to unravel CR determinants, overall survival (OS), and time to recurrence (TTR) using clinical and targeted sequencing data. Analyzing 402 patients undergoing preoperative treatment, tumor stage, size, and treatment emerged as robust response predictors. CR rates were higher in smaller, early-stage, and intensively treated tumors. Targeted sequencing analyzed 216 cases, while 120 patients provided hotspot mutation data. KRAS mutation dramatically reduced CR odds by over 50% (odds ratio [OR] = 0.3 in the targeted sequencing and OR = 0.4 hotspot cohorts, respectively). In contrast, SMAD4 and SYNE1 mutations were associated with higher CR rates (OR = 6.0 and 6.8, respectively). Favorable OS was linked to younger age, CR, and low baseline carcinoembryonic antigen levels. Notably, CR and an APC mutation increased TTR, while a BRAF mutation negatively affected TTR. Beyond tumor burden, SMAD4 and SYNE1 mutations significantly influenced CR. KRAS mutations independently correlated with radiotherapy resistance, and BRAF mutations heightened recurrence risk. Intriguingly, non-responding tumors with initially small sizes carried a higher risk of recurrence. The findings, even if limited in addition to the imperfect clinical factors, offer insights into rectal cancer treatment response, guiding personalized therapeutic strategies. By uncovering factors impacting CR, OS, and TTR, this study underscores the importance of tailored approaches for rectal cancer patients. These findings, based on extensive analysis and mutation data, pave the way for personalized interventions, optimizing outcomes in the challenges of rectal cancer preoperative treatment.", "doi": "10.1002/ijc.34880", "pmid": "38376070", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2024-11-05T07:25:22.269Z", "modified": "2025-02-28T14:10:15.877Z"}, {"entity": "publication", "iuid": "a7b95601e1624e01bd4b575456747c8d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a7b95601e1624e01bd4b575456747c8d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a7b95601e1624e01bd4b575456747c8d"}}, "title": "Metastasis and recurrence patterns in the molecular subtypes of urothelial bladder cancer.", "authors": [{"family": "Sj\u00f6dahl", "given": "Gottfrid", "initials": "G", "orcid": "0000-0002-7869-0473", "researcher": {"href": "https://publications.scilifelab.se/researcher/8997407392384ebd9eaa2ee8ee4f1435.json"}}, {"family": "Eriksson", "given": "Pontus", "initials": "P"}, {"family": "Holmsten", "given": "Karin", "initials": "K"}, {"family": "Abrahamsson", "given": "Johan", "initials": "J"}, {"family": "H\u00f6glund", "given": "Mattias", "initials": "M"}, {"family": "Bernardo", "given": "Carina", "initials": "C"}, {"family": "Ull\u00e9n", "given": "Anders", "initials": "A"}, {"family": "Liedberg", "given": "Fredrik", "initials": "F", "orcid": "0000-0001-8193-0370", "researcher": {"href": "https://publications.scilifelab.se/researcher/27b0b5f6fcdf4829ae9fd53ee7f5044c.json"}}], "type": "journal article", "published": "2024-01-01", "journal": {"title": "Int. J. Cancer", "issn": "1097-0215", "volume": "154", "issue": "1", "pages": "180-190", "issn-l": "0020-7136"}, "abstract": "Urothelial cancer of the urinary bladder frequently metastasizes to lymph-nodes, lungs, liver and bone. A taxonomy for molecular classification exists, but it is unknown if molecular subtypes show tropism for different organs. Here, we study 146 patients with de novo metastatic disease or recurrence after curative treatment. We classify primary tumors using two transcriptomic methods and immunostaining and identify enrichment and depletion of metastatic sites in molecular subtypes using permutation tests. We observed significant depletion of bone metastases in the Basal/squamous molecular subtype, whereas the Urothelial-like subtype entailed an enrichment for metastases to bone. The Genomically unstable subtype was depleted of lung metastases, but enriched for atypical sites, including six out of seven patients with brain metastases. Stroma-rich primary tumor samples were associated with local recurrence, but not with distant sites. Additionally, the proportion with brain or testis metastases differed between systemic chemotherapy regimens (GC vs MVAC) suggesting a sanctuary effect. In conclusion, molecular subtypes of urothelial bladder cancer are significantly associated with specific metastatic sites, suggesting that subtype-specific molecular determinants could exist at various steps in the metastatic cascade.", "doi": "10.1002/ijc.34715", "pmid": "37671617", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [], "notes": [], "created": "2024-11-16T05:49:01.435Z", "modified": "2024-11-16T05:49:01.539Z"}, {"entity": "publication", "iuid": "14a0f185d8d9469abfa181004e3f69c2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/14a0f185d8d9469abfa181004e3f69c2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/14a0f185d8d9469abfa181004e3f69c2"}}, "title": "An induced pluripotent stem cell t(7;12)(q36;p13) acute myeloid leukemia model shows high expression of MNX1 and a block in differentiation of the erythroid and megakaryocytic lineages.", "authors": [{"family": "Nilsson", "given": "Tina", "initials": "T"}, {"family": "Waraky", "given": "Ahmed", "initials": "A"}, {"family": "\u00d6stlund", "given": "Anders", "initials": "A"}, {"family": "Li", "given": "Susann", "initials": "S"}, {"family": "Staffas", "given": "Anna", "initials": "A"}, {"family": "Asp", "given": "Julia", "initials": "J"}, {"family": "Fogelstrand", "given": "Linda", "initials": "L"}, {"family": "Abrahamsson", "given": "Jonas", "initials": "J"}, {"family": "Palmqvist", "given": "Lars", "initials": "L", "orcid": "0000-0001-9274-360X", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e50c0057dcb47f39e085b16580806c2.json"}}], "type": "journal article", "published": "2022-09-01", "journal": {"title": "Int. J. Cancer", "issn": "1097-0215", "issn-l": "0020-7136", "volume": "151", "issue": "5", "pages": "770-782"}, "abstract": "Acute myeloid leukemia (AML) results from aberrant hematopoietic processes and these changes are frequently initiated by chromosomal translocations. One particular subtype, AML with translocation t(7;12)(q36;p13), is found in children diagnosed before 2 years of age. The mechanisms for leukemogenesis induced by t(7;12) is not understood, in part because of the lack of efficient methods to reconstruct the leukemia-associated genetic aberration with correct genomic architecture and regulatory elements. We therefore created induced pluripotent stem cell (iPSC) lines that carry the translocation t(7;12) using CRISPR/Cas9. These t(7;12) iPSC showed propensity to differentiate into all three germ layers, confirming retained stem cell properties. The potential for differentiation into hematopoietic stem and progenitor cells (HSPC) was shown by expression of CD34, CD43 and CD45. Compared with the parental iPSC line, a significant decrease in cells expressing CD235a and CD41a was seen in the t(7;12) iPSC-derived HSPC (iHSPC), suggesting a block in differentiation. Moreover, colony formation assay showed an accumulation of cells at the erythroid and myeloid progenitor stages. Gene expression analysis revealed significant down-regulation of genes associated with megakaryocyte differentiation and up-regulation of genes associated with myeloid pathways but also genes typically seen in AML cases with t(7;12). Thus, this iPSC t(7;12) leukemia model of the t(7;12) AML subtype constitutes a valuable tool for further studies of the mechanisms for leukemia development and to find new treatment options.", "doi": "10.1002/ijc.34122", "pmid": "35583991", "labels": {"Clinical Genomics Gothenburg": "Technology development", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Technology development"}, "xrefs": [{"db": "pmc", "key": "PMC9545334"}], "notes": [], "created": "2022-11-09T15:38:51.842Z", "modified": "2024-01-16T13:48:35.034Z"}, {"entity": "publication", "iuid": "b9ed712b3ac744dca1d4ef9b11d98931", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b9ed712b3ac744dca1d4ef9b11d98931.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b9ed712b3ac744dca1d4ef9b11d98931"}}, "title": "Regulatory networks and 5' partner usage of miRNA host gene fusions in breast cancer.", "authors": [{"family": "Hafsta\u00f0", "given": "V\u00f6lundur", "initials": "V"}, {"family": "S\u00f8kilde", "given": "Rolf", "initials": "R"}, {"family": "H\u00e4kkinen", "given": "Jari", "initials": "J"}, {"family": "Larsson", "given": "Malin", "initials": "M"}, {"family": "Vallon-Christersson", "given": "Johan", "initials": "J"}, {"family": "Rovira", "given": "Carlos", "initials": "C", "orcid": "0000-0002-3837-8610", "researcher": {"href": "https://publications.scilifelab.se/researcher/600b17f8de26492fa976d4d1ee1ac26b.json"}}, {"family": "Persson", "given": "Helena", "initials": "H", "orcid": "0000-0002-5187-6446", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae575945751541f7ac2a7607342a407e.json"}}], "type": "journal article", "published": "2022-07-01", "journal": {"title": "Int. J. Cancer", "issn": "1097-0215", "volume": "151", "issue": "1", "pages": "95-106", "issn-l": "0020-7136"}, "abstract": "Genomic rearrangements in cancer cells can create gene fusions where the juxtaposition of two different genes leads to the production of chimeric proteins or altered gene expression through promoter-swapping. We have previously shown that fusion transcripts involving microRNA (miRNA) host genes contribute to deregulation of miRNA expression regardless of the protein-coding potential of these transcripts. Many different genes can also be used as 5' partners by a miRNA host gene in what we named recurrent miRNA-convergent fusions. Here, we have explored the properties of 5' partners in fusion transcripts that involve miRNA hosts in breast tumours from The Cancer Genome Atlas (TCGA). We hypothesised that firstly, 5' partner genes should belong to pathways and transcriptional programmes that reflect the tumour phenotype and secondly, there should be a selection for fusion events that shape miRNA expression to benefit the tumour cell through the known hallmarks of cancer. We found that the set of 5' partners in miRNA host fusions is non-random, with overrepresentation of highly expressed genes in pathways active in cancer including epithelial-to-mesenchymal transition, translational regulation and oestrogen signalling. Furthermore, many miRNAs were upregulated in samples with host gene fusions, including established oncogenic miRNAs such as mir-21 and the mir-106b~mir-93~mir-25 cluster. To the list of mechanisms for deregulation of miRNA expression, we have added fusion transcripts that change the promoter region. We propose that this adds material for genetic selection and tumour evolution in cancer cells and that miRNA host fusions can act as tumour 'drivers'.", "doi": "10.1002/ijc.33972", "pmid": "35182081", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC9303785"}], "notes": [], "created": "2022-03-02T08:42:59.870Z", "modified": "2024-01-16T13:48:35.926Z"}, {"entity": "publication", "iuid": "a0c7031690744d69bd94427f6d63b73c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a0c7031690744d69bd94427f6d63b73c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a0c7031690744d69bd94427f6d63b73c"}}, "title": "Genome-wide estrogen receptor \u03b2 chromatin binding in human colon cancer cells reveals its tumor suppressor activity.", "authors": [{"family": "Indukuri", "given": "Rajitha", "initials": "R", "orcid": "0000-0001-6570-842X", "researcher": {"href": "https://publications.scilifelab.se/researcher/94148ec0ffb74f9bb0243c18a1256c22.json"}}, {"family": "Jafferali", "given": "Mohammed Hakim", "initials": "MH"}, {"family": "Song", "given": "Dandan", "initials": "D"}, {"family": "Damdimopoulos", "given": "Anastasios", "initials": "A"}, {"family": "Hases", "given": "Linnea", "initials": "L"}, {"family": "Zhao", "given": "Chunyan", "initials": "C"}, {"family": "Archer", "given": "Amena", "initials": "A", "orcid": "0000-0002-0400-4151", "researcher": {"href": "https://publications.scilifelab.se/researcher/4502538fe3e84cb6a6618c972fa10b08.json"}}, {"family": "Williams", "given": "Cecilia", "initials": "C", "orcid": "0000-0002-0602-2062", "researcher": {"href": "https://publications.scilifelab.se/researcher/89989da8d4e64dd3a30b87fc62ceefae.json"}}], "type": "journal article", "published": "2021-08-01", "journal": {"title": "Int. J. Cancer", "issn": "1097-0215", "volume": "149", "issue": "3", "pages": "692-706", "issn-l": "0020-7136"}, "abstract": "Colorectal cancer (CRC) is the third leading cause of cancer death in the western world. In women, menopausal hormone therapy has been shown to reduce CRC incidence by 20%. Studies demonstrate that estrogen activating estrogen receptor beta (ER\u03b2) protects against CRC. ER\u03b2 is a nuclear receptor that regulates gene expression through interactions with the chromatin. This molecular mechanism is, however, not well characterized in colon. Here, we present for the first time, the cistrome of ER\u03b2 in different colon cancer cell lines. We use cell lines engineered to express ER\u03b2, optimize and validate an ER\u03b2 antibody for chromatin-immunoprecipitation (ChIP), and perform ChIP-Seq. We identify key binding motifs, including ERE, AP-1, and TCF sites, and we determine enrichment of binding to cis-regulatory chromatin sites of genes involved in tumor development, cell migration, cell adhesion, apoptosis, and Wnt signaling pathways. We compare the corresponding cistromes of colon and breast cancer and find that they are conserved for about a third of genes, including GREB1, but that ER\u03b2 tethering to TCF and KLF family motifs is characteristic for colon. We exemplify upregulation of putative CRC tumor suppressor gene CST5 where ER\u03b2 in colon cells binds to cis-regulatory regions nearby (-351 bp) the transcriptional start site. Our work provides a foundation for understanding the mechanism of action of ER\u03b2 in CRC prevention.", "doi": "10.1002/ijc.33573", "pmid": "33754337", "labels": {"NGI Stockholm (Genomics Production)": null, "NGI Stockholm (Genomics Applications)": null, "National Genomics Infrastructure": null, "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2021-06-09T12:16:18.247Z", "modified": "2024-01-16T13:48:38.912Z"}, {"entity": "publication", "iuid": "48b0fb0b1902402caae10d57d86fc5ef", "links": {"self": {"href": "https://publications.scilifelab.se/publication/48b0fb0b1902402caae10d57d86fc5ef.json"}, "display": {"href": "https://publications.scilifelab.se/publication/48b0fb0b1902402caae10d57d86fc5ef"}}, "title": "Association between breast cancer risk and disease aggressiveness: Characterizing underlying gene expression patterns.", "authors": [{"family": "Ugalde-Morales", "given": "Emilio", "initials": "E", "orcid": "0000-0002-3201-6416", "researcher": {"href": "https://publications.scilifelab.se/researcher/3e2e77664f574b95aeae3c5d14f31de5.json"}}, {"family": "Grassmann", "given": "Felix", "initials": "F", "orcid": "0000-0003-1390-7528", "researcher": {"href": "https://publications.scilifelab.se/researcher/76a190980d904236914679e88737706b.json"}}, {"family": "Humphreys", "given": "Keith", "initials": "K"}, {"family": "Li", "given": "Jingmei", "initials": "J", "orcid": "0000-0001-8587-7511", "researcher": {"href": "https://publications.scilifelab.se/researcher/ee0aa1afe3af4dcba58f07c8c19d11e0.json"}}, {"family": "Eriksson", "given": "Mikael", "initials": "M"}, {"family": "Tobin", "given": "Nicholas P", "initials": "NP"}, {"family": "Borg", "given": "\u00c5ke", "initials": "\u00c5"}, {"family": "Vallon-Christersson", "given": "Johan", "initials": "J"}, {"family": "Hall", "given": "Per", "initials": "P"}, {"family": "Czene", "given": "Kamila", "initials": "K"}], "type": "journal article", "published": "2021-02-15", "journal": {"title": "Int. J. Cancer", "issn": "1097-0215", "volume": "148", "issue": "4", "pages": "884-894", "issn-l": "0020-7136"}, "abstract": "The association between breast cancer risk defined by the Tyrer-Cuzick score (TC) and disease prognosis is not well established. Here, we investigated the relationship between 5-year TC and disease aggressiveness and then characterized underlying molecular processes. In a case-only study (n = 2474), we studied the association of TC with molecular subtypes and tumor characteristics. In a subset of patients (n = 672), we correlated gene expression to TC and computed a low-risk TC gene expression (TC-Gx) profile, that is, a profile expected to be negatively associated with risk, which we used to test for association with disease aggressiveness. We performed enrichment analysis to pinpoint molecular processes likely to be altered in low-risk tumors. A higher TC was found to be inversely associated with more aggressive surrogate molecular subtypes and tumor characteristics (P < .05) including Ki-67 proliferation status (P < 5 \u00d7 10-07 ). Our low-risk TC-Gx, based on the weighted sum of 37 expression values of genes strongly correlated with TC, was associated with basal-like (P < 5 \u00d7 10-13 ), HER2-enriched subtype (P < 5 \u00d7 10-07 ) and worse 10-year breast cancer-specific survival (log-rank P < 5 \u00d7 10-04 ). Associations between low-risk TC-Gx and more aggressive molecular subtypes were replicated in an independent cohort from The Cancer Genome Atlas database (n = 975). Gene expression that correlated with low TC was enriched in proliferation and oncogenic signaling pathways (FDR < 0.05). Moreover, higher proliferation was a key factor explaining the association with worse survival. Women who developed breast cancer despite having a low risk were diagnosed with more aggressive tumors and had a worse prognosis, most likely driven by increased proliferation. Our findings imply the need to establish risk factors associated with more aggressive breast cancer subtypes.", "doi": "10.1002/ijc.33270", "pmid": "32856720", "labels": {"Bioinformatics Support and Infrastructure": "Service", "Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7818270"}], "notes": [], "created": "2020-09-30T10:33:48.257Z", "modified": "2021-11-10T12:26:58.196Z"}, {"entity": "publication", "iuid": "a0dda33b98ee48789e7ac7a800a80bb5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a0dda33b98ee48789e7ac7a800a80bb5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a0dda33b98ee48789e7ac7a800a80bb5"}}, "title": "Pericyte dysfunction due to Shb gene deficiency increases B16F10 melanoma lung metastasis.", "authors": [{"family": "He", "given": "Qi", "initials": "Q"}, {"family": "Li", "given": "Xiujuan", "initials": "X"}, {"family": "He", "given": "Liqun", "initials": "L"}, {"family": "Li", "given": "Yousheng", "initials": "Y"}, {"family": "Betsholtz", "given": "Christer", "initials": "C"}, {"family": "Welsh", "given": "Michael", "initials": "M", "orcid": "0000-0002-5467-9755", "researcher": {"href": "https://publications.scilifelab.se/researcher/c01673aeb9be429c80da30d5407b2725.json"}}], "type": "journal article", "published": "2020-11-01", "journal": {"title": "Int. J. Cancer", "issn": "1097-0215", "volume": "147", "issue": "9", "pages": "2634-2644", "issn-l": "0020-7136"}, "abstract": "Intravasation, vascular dissemination and metastasis of malignant tumor cells require their passage through the vascular wall which is commonly composed of pericytes and endothelial cells. We currently decided to investigate the relative contribution of these cell types to B16F10 melanoma metastasis in mice using an experimental model of host Shb gene (Src homology 2 domain-containing protein B) inactivation. Conditional inactivation of Shb in endothelial cells using Cdh5-CreERt2 resulted in decreased tumor growth, reduced vascular leakage, increased hypoxia and no effect on pericyte coverage and lung metastasis. RNAseq of tumor endothelial cells from these mice revealed changes in cellular components such as adherens junctions and focal adhesions by gene ontology analysis that were in line with the observed effects on leakage and junction morphology. Conditional inactivation of Shb in pericytes using Pdgfrb-CreERt2 resulted in decreased pericyte coverage of small tumor vessels with lumen, increased leakage, aberrant platelet-derived growth factor receptor B (PDGFRB) signaling and a higher frequency of lung metastasis without concomitant effects on tumor growth or oxygenation. Flow cytometry failed to reveal immune cell alterations that could explain the metastatic phenotype in this genetic model of Shb deficiency. It is concluded that proper pericyte function plays a significant role in suppressing B16F10 lung metastasis.", "doi": "10.1002/ijc.33110", "pmid": "32441314", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2020-12-08T23:56:20.495Z", "modified": "2024-01-16T13:48:41.445Z"}, {"entity": "publication", "iuid": "4b7ea1ee885748268299dace9908513e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4b7ea1ee885748268299dace9908513e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4b7ea1ee885748268299dace9908513e"}}, "title": "Molecular changes during progression from nonmuscle invasive to advanced urothelial carcinoma.", "authors": [{"family": "Sj\u00f6dahl", "given": "Gottfrid", "initials": "G", "orcid": "0000-0002-7869-0473", "researcher": {"href": "https://publications.scilifelab.se/researcher/8997407392384ebd9eaa2ee8ee4f1435.json"}}, {"family": "Eriksson", "given": "Pontus", "initials": "P"}, {"family": "Patschan", "given": "Oliver", "initials": "O"}, {"family": "Marzouka", "given": "Nour-Al-Dain", "initials": "NA"}, {"family": "Jakobsson", "given": "Lovisa", "initials": "L"}, {"family": "Bernardo", "given": "Carina", "initials": "C"}, {"family": "L\u00f6vgren", "given": "Kristina", "initials": "K"}, {"family": "Chebil", "given": "Gunilla", "initials": "G"}, {"family": "Zwarthoff", "given": "Ellen", "initials": "E"}, {"family": "Liedberg", "given": "Fredrik", "initials": "F"}, {"family": "H\u00f6glund", "given": "Mattias", "initials": "M"}], "type": "journal article", "published": "2020-05-01", "journal": {"title": "Int. J. Cancer", "issn": "1097-0215", "volume": "146", "issue": "9", "pages": "2636-2647", "issn-l": "0020-7136"}, "abstract": "Molecular changes occurring during invasion and clinical progression of cancer are difficult to study longitudinally in patient-derived material. A unique feature of urothelial bladder cancer (UBC) is that patients frequently develop multiple nonmuscle invasive tumors, some of which may eventually progress to invade the muscle of the bladder wall. Here, we use a cohort of 73 patients that experienced a total of 357 UBC diagnoses to study the stability or change in detected molecular alterations during cancer progression. The tumors were subtyped by gene expression profiling and analyzed for hotspot mutations in FGFR3, PIK3CA and TERT, the most frequent early driver mutations in this tumor type. TP53 alterations, frequent in advanced UBC, were inferred from p53 staining pattern, and potential genomic alterations were inferred by gene expression patterns at regions harboring frequent copy number alterations. We show that early driver mutations were largely preserved in UBC recurrences. Changes in FGFR3, PIK3CA or TERT mutation status were not linked to changes in molecular subtype and aggressive behavior. Instead, changes into a more aggressive molecular subtype seem to be associated with p53 alterations. We analyze changes in gene expression from primary tumors, to recurrences and progression tumors, and identify two modes of progression: Patients for whom progression is preceded by or coincides with a radical subtype shift, and patients who progress without any systematic molecular changes. For the latter group of patients, progression may be either stochastic or depending on factors already present at primary tumor initiation.", "doi": "10.1002/ijc.32737", "pmid": "31609466", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7079000"}], "notes": [], "created": "2021-11-25T09:36:06.632Z", "modified": "2021-11-25T09:36:06.692Z"}, {"entity": "publication", "iuid": "39682f91aeb14ea7b76502635c21251f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/39682f91aeb14ea7b76502635c21251f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/39682f91aeb14ea7b76502635c21251f"}}, "title": "Integrated epigenomic and transcriptomic analysis reveals TP63 as a novel player in clinically aggressive chronic lymphocytic leukemia.", "authors": [{"family": "Papakonstantinou", "given": "Nikos", "initials": "N"}, {"family": "Ntoufa", "given": "Stavroula", "initials": "S"}, {"family": "Tsagiopoulou", "given": "Maria", "initials": "M"}, {"family": "Moysiadis", "given": "Theodoros", "initials": "T"}, {"family": "Bhoi", "given": "Sujata", "initials": "S"}, {"family": "Malousi", "given": "Andigoni", "initials": "A"}, {"family": "Psomopoulos", "given": "Fotis", "initials": "F"}, {"family": "Mansouri", "given": "Larry", "initials": "L"}, {"family": "Laidou", "given": "Stamatia", "initials": "S"}, {"family": "Papazoglou", "given": "Despoina", "initials": "D"}, {"family": "Gounari", "given": "Maria", "initials": "M"}, {"family": "Pasentsis", "given": "Konstantinos", "initials": "K"}, {"family": "Plevova", "given": "Karla", "initials": "K"}, {"family": "Kuci-Emruli", "given": "Venera", "initials": "V"}, {"family": "Duran-Ferrer", "given": "Marti", "initials": "M"}, {"family": "Davis", "given": "Zadie", "initials": "Z"}, {"family": "Ek", "given": "Sara", "initials": "S"}, {"family": "Rossi", "given": "Davide", "initials": "D"}, {"family": "Gaidano", "given": "Gianluca", "initials": "G"}, {"family": "Ritgen", "given": "Matthias", "initials": "M"}, {"family": "Oscier", "given": "David", "initials": "D"}, {"family": "Stavroyianni", "given": "Niki", "initials": "N"}, {"family": "Pospisilova", "given": "Sarka", "initials": "S"}, {"family": "Davi", "given": "Frederic", "initials": "F"}, {"family": "Ghia", "given": "Paolo", "initials": "P"}, {"family": "Hadzidimitriou", "given": "Anastasia", "initials": "A"}, {"family": "Belessi", "given": "Chrysoula", "initials": "C"}, {"family": "Martin-Subero", "given": "Jose I", "initials": "JI"}, {"family": "Pott", "given": "Christiane", "initials": "C"}, {"family": "Rosenquist", "given": "Richard", "initials": "R"}, {"family": "Stamatopoulos", "given": "Kostas", "initials": "K", "orcid": "0000-0001-8529-640X", "researcher": {"href": "https://publications.scilifelab.se/researcher/772756566c154559b2c70c8f0f44d1ad.json"}}], "type": "journal article", "published": "2019-06-01", "journal": {"volume": "144", "issn": "1097-0215", "issue": "11", "pages": "2695-2706", "title": "Int. J. Cancer", "issn-l": "0020-7136"}, "abstract": "Chronic lymphocytic leukemia (CLL) stereotyped subsets #6 and #8 include cases expressing unmutated B cell receptor immunoglobulin (BcR IG) (U-CLL). Subset #6 (IGHV1-69/IGKV3-20) is less aggressive compared to subset #8 (IGHV4-39/IGKV1(D)-39) which has the highest risk for Richter's transformation among all CLL. The underlying reasons for this divergent clinical behavior are not fully elucidated. To gain insight into this issue, here we focused on epigenomic signatures and their links with gene expression, particularly investigating genome-wide DNA methylation profiles in subsets #6 and #8 as well as other U-CLL cases not expressing stereotyped BcR IG. We found that subset #8 showed a distinctive DNA methylation profile compared to all other U-CLL cases, including subset #6. Integrated analysis of DNA methylation and gene expression revealed significant correlation for several genes, particularly highlighting a relevant role for the TP63 gene which was hypomethylated and overexpressed in subset #8. This observation was validated by quantitative PCR, which also revealed TP63 mRNA overexpression in additional nonsubset U-CLL cases. BcR stimulation had distinct effects on p63 protein expression, particularly leading to induction in subset #8, accompanied by increased CLL cell survival. This pro-survival effect was also supported by siRNA-mediated downregulation of p63 expression resulting in increased apoptosis. In conclusion, we report that DNA methylation profiles may vary even among CLL patients with similar somatic hypermutation status, supporting a compartmentalized approach to dissecting CLL biology. Furthermore, we highlight p63 as a novel prosurvival factor in CLL, thus identifying another piece of the complex puzzle of clinical aggressiveness.", "doi": "10.1002/ijc.31999", "pmid": "30447004", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [], "notes": [], "created": "2019-01-14T11:51:16.832Z", "modified": "2021-06-21T14:00:35.291Z"}, {"entity": "publication", "iuid": "e0e299f2920c45afa3763b218f36089f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e0e299f2920c45afa3763b218f36089f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e0e299f2920c45afa3763b218f36089f"}}, "title": "Expression of scavenger receptor MARCO defines a targetable tumor-associated macrophage subset in non-small cell lung cancer.", "authors": [{"family": "La Fleur", "given": "Linn\u00e9a", "initials": "L"}, {"family": "Boura", "given": "Vanessa F", "initials": "VF"}, {"family": "Alexeyenko", "given": "Andrey", "initials": "A"}, {"family": "Berglund", "given": "Anders", "initials": "A"}, {"family": "Pont\u00e9n", "given": "Victor", "initials": "V"}, {"family": "Mattsson", "given": "Johanna S M", "initials": "JSM"}, {"family": "Djureinovic", "given": "Dijana", "initials": "D"}, {"family": "Persson", "given": "Johan", "initials": "J"}, {"family": "Brunnstr\u00f6m", "given": "Hans", "initials": "H"}, {"family": "Isaksson", "given": "Johan", "initials": "J"}, {"family": "Brand\u00e9n", "given": "Eva", "initials": "E"}, {"family": "Koyi", "given": "Hirsh", "initials": "H"}, {"family": "Micke", "given": "Patrick", "initials": "P"}, {"family": "Karlsson", "given": "Mikael C I", "initials": "MCI"}, {"family": "Botling", "given": "Johan", "initials": "J"}], "type": "journal article", "published": "2018-04-18", "journal": {"volume": null, "issn": "1097-0215", "issue": null, "pages": null, "title": "Int. J. Cancer", "issn-l": "0020-7136"}, "abstract": "Tumor-associated macrophages (TAMs) are attractive targets for immunotherapy. Recently, studies in animal models showed that treatment with an anti-TAM antibody directed against the scavenger receptor MARCO resulted in suppression of tumor growth and metastatic dissemination. Here we investigated the expression of MARCO in relation to other macrophage markers and immune pathways in a non-small cell lung cancer (NSCLC) cohort (n\u2009=\u2009352). MARCO, CD68, CD163, MSR1 and programmed death ligand-1 (PD-L1) were analyzed by immunohistochemistry and immunofluorescence, and associations to other immune cells and regulatory pathways were studied in a subset of cases (n\u2009=\u2009199) with available RNA-seq data. We observed a large variation in macrophage density between cases and a strong correlation between CD68 and CD163, suggesting that the majority of TAMs present in NSCLC exhibit a protumor phenotype. Correlation to clinical data only showed a weak trend toward worse survival for patients with high macrophage infiltration. Interestingly, MARCO was expressed on a distinct subpopulation of TAMs, which tended to aggregate in close proximity to tumor cell nests. On the transcriptomic level, we found a positive association between MARCO gene expression and general immune response pathways including strong links to immunosuppressive TAMs, T-cell infiltration and immune checkpoint molecules. Indeed, a higher macrophage infiltration was seen in tumors expressing PD-L1, and macrophages residing within tumor cell nests co-expressed MARCO and PD-L1. Thus, MARCO is a potential new immune target for anti-TAM treatment in a subset of NSCLC patients, possibly in combination with available immune checkpoint inhibitors.", "doi": "10.1002/ijc.31545", "pmid": "29667169", "labels": {"Clinical Genomics Uppsala": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics Support and Infrastructure": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Service", "Clinical Genomics": "Collaborative"}, "xrefs": [], "notes": [], "created": "2018-10-31T19:47:13.069Z", "modified": "2024-01-16T13:48:46.503Z"}, {"entity": "publication", "iuid": "d658f4b23c4346fd9fe015e04165cfed", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d658f4b23c4346fd9fe015e04165cfed.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d658f4b23c4346fd9fe015e04165cfed"}}, "title": "A prognosis based classification of undifferentiated uterine sarcomas: identification of mitotic index, hormone receptors and YWHAE-FAM22 translocation status as predictors of survival.", "authors": [{"family": "Gremel", "given": "Gabriela", "initials": "G"}, {"family": "Liew", "given": "Markus", "initials": "M"}, {"family": "Hamzei", "given": "Farzaneh", "initials": "F"}, {"family": "Hardell", "given": "Elin", "initials": "E"}, {"family": "Selling", "given": "Jonas", "initials": "J"}, {"family": "Ghaderi", "given": "Mehran", "initials": "M"}, {"family": "Stemme", "given": "Sten", "initials": "S"}, {"family": "Pont\u00e9n", "given": "Fredrik", "initials": "F"}, {"family": "Carlson", "given": "Joseph W", "initials": "JW"}], "type": "journal article", "published": "2015-04-01", "journal": {"volume": "136", "issn": "1097-0215", "issue": "7", "pages": "1608-1618", "title": "Int. J. Cancer", "issn-l": "0020-7136"}, "abstract": "Undifferentiated uterine sarcomas (UUS) are rare tumors with a heterologous biology and a poor prognosis. The goal of this study was to examine clinicopathology, biomarkers and YWHAE-FAM22 translocation status, in the prognosis of these tumors. Twenty-six cases of UUS were included. All original slides were rereviewed and age at diagnosis, tumor stage, \"Kurihara\" diagnosis, mitotic index, presence of necrosis and grade of nuclear atypia were recorded. Additionally, a tissue microarray was constructed from 22 of the cases, and the protein biomarkers P53, P16, Ki-67, Cyclin-D1, ER, PR and ANLN were evaluated by immunohistochemistry. All tumors were evaluated for the presence of a YWHAE-FAM translocation; the translocation was demonstrated in the three Cyclin-D1 positive tumors. Follow-up data in the form of overall survival were available on all patients. These tumors could be divided into two prognostic groups, a high mitotic index group (10 cases, M\u2009=\u200936.8, SD\u2009=\u20095.4) and a low mitotic index group (16 cases, M\u2009=\u20098.7, SD\u2009=\u20095.8). These two groups showed a statistically significant difference in prognosis. The expression of ER, PR or presence of the YWHAE-FAM22 translocation correlated with low mitotic index and an additionally improved prognosis, although the number of cases was small. These results indicate that UUS can be divided into two prognostic groups using mitotic index as a primary criteria, followed by expression of either ER, PR or the presence of a YWHAE-FAM22 translocation as a secondary criteria. This study demonstrates the presence of statistically significant prognostic subgroups within UUS, and provides treatment insights.", "doi": "10.1002/ijc.29141", "pmid": "25130488", "labels": {"Tissue Profiling": null}, "xrefs": [], "notes": [], "created": "2017-05-04T14:56:05.983Z", "modified": "2017-05-30T12:57:35.693Z"}, {"entity": "publication", "iuid": "621fe62e399d49dd99e3ab8a719e3299", "links": {"self": {"href": "https://publications.scilifelab.se/publication/621fe62e399d49dd99e3ab8a719e3299.json"}, "display": {"href": "https://publications.scilifelab.se/publication/621fe62e399d49dd99e3ab8a719e3299"}}, "title": "Aberrantly activated claudin 6 and 18.2 as potential therapy targets in non-small-cell lung cancer.", "authors": [{"family": "Micke", "given": "Patrick", "initials": "P"}, {"family": "Mattsson", "given": "Johanna Sofia Margareta", "initials": "JS"}, {"family": "Edlund", "given": "Karolina", "initials": "K"}, {"family": "Lohr", "given": "Miriam", "initials": "M"}, {"family": "Jirstr\u00f6m", "given": "Karin", "initials": "K"}, {"family": "Berglund", "given": "Anders", "initials": "A"}, {"family": "Botling", "given": "Johan", "initials": "J"}, {"family": "Rahnenfuehrer", "given": "J\u00f6rg", "initials": "J"}, {"family": "Marincevic", "given": "Millaray", "initials": "M"}, {"family": "Pont\u00e9n", "given": "Fredrik", "initials": "F"}, {"family": "Ekman", "given": "Simon", "initials": "S"}, {"family": "Hengstler", "given": "Jan", "initials": "J"}, {"family": "W\u00f6ll", "given": "Stefan", "initials": "S"}, {"family": "Sahin", "given": "Ugur", "initials": "U"}, {"family": "T\u00fcreci", "given": "Ozlem", "initials": "O"}], "type": "journal article", "published": "2014-11-01", "journal": {"volume": "135", "issn": "1097-0215", "issue": "9", "pages": "2206-2214", "title": "Int. J. Cancer", "issn-l": "0020-7136"}, "abstract": "Claudins (CLDNs) are central components of tight junctions that regulate epithelial-cell barrier function and polarity. Altered CLDN expression patterns have been demonstrated in numerous cancer types and lineage-specific CLDNs have been proposed as therapy targets. The objective of this study was to assess which fraction of patients with non-small-cell lung cancer (NSCLC) express CLDN6 and CLDN18 isoform 2 (CLDN18.2). Protein expression of CLDN6 and CLDN18.2 was examined by immunohistochemistry on a tissue microarray (n\u2009=\u2009355) and transcript levels were supportively determined based on gene expression microarray data from fresh-frozen NSCLC tissues (n\u2009=\u2009196). Both were analyzed with regard to frequency, distribution and association with clinical parameters. Immunohistochemical analysis of tissue sections revealed distinct membranous positivity of CLDN6 (6.5%) and CLDN18.2 (3.7%) proteins in virtually non-overlapping subgroups of adenocarcinomas and large-cell carcinomas. Pneumocytes and bronchial epithelial cells were consistently negative. Corresponding to the protein expression, in subsets of non-squamous lung carcinoma high mRNA levels of CLDN6 (7-16%) and total CLDN18 (5-12%) were observed. Protein expression correlated well with total mRNA expression of the corresponding gene (rho\u2009=\u20090.4-0.8). CLDN18.2 positive tumors were enriched among slowly proliferating, thyroid transcription factor 1 (TTF-1)-negative adenocarcinomas, suggesting that isoform-specific CLDN expression may delineate a specific subtype. Noteworthy, high CLDN6 protein expression was associated with worse prognosis in lung adenocarcinoma in the univariate [hazard ratio (HR): 1.8; p\u2009=\u20090.03] and multivariate COX regression model (HR: 1.9; p\u2009=\u20090.02). These findings encourage further clinical exploration of targeting ectopically activated CLDN expression as a valuable treatment concept in NSCLC.", "doi": "10.1002/ijc.28857", "pmid": "24710653", "labels": {"Tissue Profiling": null}, "xrefs": [], "notes": [], "created": "2017-05-04T14:56:06.282Z", "modified": "2017-05-30T12:54:28.811Z"}, {"entity": "publication", "iuid": "1997c4840801487f8f2ff1f6fc46f393", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1997c4840801487f8f2ff1f6fc46f393.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1997c4840801487f8f2ff1f6fc46f393"}}, "title": "Exome sequencing reveals frequent inactivating mutations in ARID1A, ARID1B, ARID2 and ARID4A in microsatellite unstable colorectal cancer.", "authors": [{"family": "Cajuso", "given": "Tatiana", "initials": "T"}, {"family": "H\u00e4nninen", "given": "Ulrika A", "initials": "UA"}, {"family": "Kondelin", "given": "Johanna", "initials": "J"}, {"family": "Gylfe", "given": "Alexandra E", "initials": "AE"}, {"family": "Tanskanen", "given": "Tomas", "initials": "T"}, {"family": "Katainen", "given": "Riku", "initials": "R"}, {"family": "Pitk\u00e4nen", "given": "Esa", "initials": "E"}, {"family": "Ristolainen", "given": "Heikki", "initials": "H"}, {"family": "Kaasinen", "given": "Eevi", "initials": "E"}, {"family": "Taipale", "given": "Minna", "initials": "M"}, {"family": "Taipale", "given": "Jussi", "initials": "J"}, {"family": "B\u00f6hm", "given": "Jan", "initials": "J"}, {"family": "Renkonen-Sinisalo", "given": "Laura", "initials": "L"}, {"family": "Mecklin", "given": "Jukka-Pekka", "initials": "JP"}, {"family": "J\u00e4rvinen", "given": "Heikki", "initials": "H"}, {"family": "Tuupanen", "given": "Sari", "initials": "S"}, {"family": "Kilpivaara", "given": "Outi", "initials": "O"}, {"family": "Vahteristo", "given": "Pia", "initials": "P"}], "type": "journal article", "published": "2014-08-01", "journal": {"volume": "135", "issn": "1097-0215", "issue": "3", "pages": "611-623", "title": "Int. J. Cancer", "issn-l": "0020-7136"}, "abstract": "ARID1A has been identified as a novel tumor suppressor gene in ovarian cancer and subsequently in various other tumor types. ARID1A belongs to the ARID domain containing gene family, which comprises of 15 genes involved, for example, in transcriptional regulation, proliferation and chromatin remodeling. In this study, we used exome sequencing data to analyze the mutation frequency of all the ARID domain containing genes in 25 microsatellite unstable (MSI) colorectal cancers (CRCs) as a first systematic effort to characterize the mutation pattern of the whole ARID gene family. Genes which fulfilled the selection criteria in this discovery set (mutations in at least 4/25 [16%] samples, including at least one nonsense or splice site mutation) were chosen for further analysis in an independent validation set of 21 MSI CRCs. We found that in addition to ARID1A, which was mutated in 39% of the tumors (18/46), also ARID1B (13%, 6/46), ARID2 (13%, 6/46) and ARID4A (20%, 9/46) were frequently mutated. In all these genes, the mutations were distributed along the entire length of the gene, thus distinguishing them from typical MSI target genes previously described. Our results indicate that in addition to ARID1A, other members of the ARID gene family may play a role in MSI CRC.", "doi": "10.1002/ijc.28705", "pmid": "24382590", "labels": {"Karolinska High Throughput Center (KHTC)": null}, "xrefs": [], "notes": [], "created": "2017-05-04T14:57:07.503Z", "modified": "2017-05-30T11:44:29.242Z"}, {"entity": "publication", "iuid": "bfd4f700d18c43ffb48bee94681c3a87", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bfd4f700d18c43ffb48bee94681c3a87.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bfd4f700d18c43ffb48bee94681c3a87"}}, "title": "A study of embryonic stem cell-related proteins in human astrocytomas: identification of Nanog as a predictor of survival.", "authors": [{"family": "Elsir", "given": "Tamador", "initials": "T"}, {"family": "Edqvist", "given": "Per-Henrik", "initials": "PH"}, {"family": "Carlson", "given": "Joseph", "initials": "J"}, {"family": "Ribom", "given": "Dan", "initials": "D"}, {"family": "Bergqvist", "given": "Michael", "initials": "M"}, {"family": "Ekman", "given": "Simon", "initials": "S"}, {"family": "Popova", "given": "Svetlana N", "initials": "SN"}, {"family": "Alafuzoff", "given": "Irina", "initials": "I"}, {"family": "Ponten", "given": "Fredrik", "initials": "F"}, {"family": "Nist\u00e9r", "given": "Monica", "initials": "M"}, {"family": "Smits", "given": "Anja", "initials": "A"}], "type": "journal article", "published": "2014-03-01", "journal": {"volume": "134", "issn": "1097-0215", "issue": "5", "pages": "1123-1131", "title": "Int. J. Cancer", "issn-l": "0020-7136"}, "abstract": "Recent studies suggest that the regulatory networks controlling the functions of stem cells during development may be abnormally active in human cancers. An embryonic stem cell (ESC) gene signature was found to correlate with a more undifferentiated phenotype of several human cancer types including gliomas, and associated with poor prognosis in breast cancer. In the present study, we used tissue microarrays of 80 low-grade (WHO Grade II) and 98 high-grade human gliomas (WHO Grades III and IV) to investigate the presence of the ESC-related proteins Nanog, Klf4, Oct4, Sox2 and c-Myc by immunohistochemistry. While similar patterns of co-expressed proteins between low- and high-grade gliomas were present, we found up-regulated protein levels of Nanog, Klf4, Oct4 and Sox2 in high-grade gliomas. Survival analysis by Kaplan-Meier analysis revealed a significant shorter survival in the subgroups of low-grade astrocytomas (n = 42) with high levels of Nanog protein (p = 0.0067) and of Klf4 protein (p = 0.0368), in high-grade astrocytomas (n = 85) with high levels of Nanog (p = 0.0042), Klf4 (p = 0.0447), and c-Myc (p = 0.0078) and in glioblastomas only (n = 71) with high levels of Nanog (p = 0.0422) and of c-Myc (p = 0.0256). In the multivariate model, Nanog was identified as an independent prognostic factor in the subgroups of low-grade astrocytomas (p = 0.0039), high-grade astrocytomas (p = 0.0124) and glioblastomas only (p = 0.0544), together with established clinical variables in these tumors. These findings provide further evidence for the joint regulatory pathways of ESC-related proteins in gliomas and identify Nanog as one of the key players in determining clinical outcome of human astrocytomas.", "doi": "10.1002/ijc.28441", "pmid": "24037901", "labels": {"Tissue Profiling": null}, "xrefs": [], "notes": [], "created": "2017-05-04T14:55:59.558Z", "modified": "2017-05-30T12:56:49.218Z"}, {"entity": "publication", "iuid": "c377029014784be6aa1c7671aa6953aa", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c377029014784be6aa1c7671aa6953aa.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c377029014784be6aa1c7671aa6953aa"}}, "title": "Novel signatures of cancer-associated fibroblasts.", "authors": [{"family": "Boz\u00f3ky", "given": "Benedek", "initials": "B"}, {"family": "Savchenko", "given": "Andrii", "initials": "A"}, {"family": "Csermely", "given": "P\u00e9ter", "initials": "P"}, {"family": "Korcsm\u00e1ros", "given": "Tam\u00e1s", "initials": "T"}, {"family": "D\u00fal", "given": "Zolt\u00e1n", "initials": "Z"}, {"family": "Pont\u00e9n", "given": "Fredrik", "initials": "F"}, {"family": "Sz\u00e9kely", "given": "L\u00e1szl\u00f3", "initials": "L"}, {"family": "Klein", "given": "George", "initials": "G"}], "type": "journal article", "published": "2013-07-15", "journal": {"volume": "133", "issn": "1097-0215", "issue": "2", "pages": "286-293", "title": "Int. J. Cancer", "issn-l": "0020-7136"}, "abstract": "Increasing evidence indicates the importance of the tumor microenvironment, in particular cancer-associated fibroblasts, in cancer development and progression. In our study, we developed a novel, visually based method to identify new immunohistochemical signatures of these fibroblasts. The method employed a protein list based on 759 protein products of genes identified by RNA profiling from our previous study, comparing fibroblasts with differential growth-modulating effect on human cancers cells, and their first neighbors in the human protein interactome. These 2,654 proteins were analyzed in the Human Protein Atlas online database by comparing their immunohistochemical expression patterns in normal versus tumor-associated fibroblasts. Twelve new proteins differentially expressed in cancer-associated fibroblasts were identified (DLG1, BHLHE40, ROCK2, RAB31, AZI2, PKM2, ARHGAP31, ARHGAP26, ITCH, EGLN1, RNF19A and PLOD2), four of them can be connected to the Rho kinase signaling pathway. They were further analyzed in several additional tumor stromata and revealed that the majority showed congruence among the different tumors. Many of them were also positive in normal myofibroblast-like cells. The new signatures can be useful in immunohistochemical analysis of different tumor stromata and may also give us an insight into the pathways activated in them in their true in vivo context. The method itself could be used for other similar analysis to identify proteins expressed in other cell types in tumors and their surrounding microenvironment.", "doi": "10.1002/ijc.28035", "pmid": "23319410", "labels": {"Tissue Profiling": null}, "xrefs": [], "notes": [], "created": "2017-05-04T14:55:59.257Z", "modified": "2017-05-30T12:56:58.377Z"}, {"entity": "publication", "iuid": "30181957b2e34c5288e3afd660451d25", "links": {"self": {"href": "https://publications.scilifelab.se/publication/30181957b2e34c5288e3afd660451d25.json"}, "display": {"href": "https://publications.scilifelab.se/publication/30181957b2e34c5288e3afd660451d25"}}, "title": "CD99 is a novel prognostic stromal marker in non-small cell lung cancer.", "authors": [{"family": "Edlund", "given": "Karolina", "initials": "K"}, {"family": "Lindskog", "given": "Cecilia", "initials": "C"}, {"family": "Saito", "given": "Akira", "initials": "A"}, {"family": "Berglund", "given": "Anders", "initials": "A"}, {"family": "Pont\u00e9n", "given": "Fredrik", "initials": "F"}, {"family": "G\u00f6ransson-Kultima", "given": "Hanna", "initials": "H"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}, {"family": "Jirstr\u00f6m", "given": "Karin", "initials": "K"}, {"family": "Planck", "given": "Maria", "initials": "M"}, {"family": "Johansson", "given": "Leif", "initials": "L"}, {"family": "Lambe", "given": "Mats", "initials": "M"}, {"family": "Holmberg", "given": "Lars", "initials": "L"}, {"family": "Nyberg", "given": "Fredrik", "initials": "F"}, {"family": "Ekman", "given": "Simon", "initials": "S"}, {"family": "Bergqvist", "given": "Michael", "initials": "M"}, {"family": "Landelius", "given": "Per", "initials": "P"}, {"family": "Lamberg", "given": "Kristina", "initials": "K"}, {"family": "Botling", "given": "Johan", "initials": "J"}, {"family": "Ostman", "given": "Arne", "initials": "A"}, {"family": "Micke", "given": "Patrick", "initials": "P"}], "type": "journal article", "published": "2012-11-15", "journal": {"volume": "131", "issn": "1097-0215", "issue": "10", "pages": "2264-2273", "title": "Int. J. Cancer", "issn-l": "0020-7136"}, "abstract": "The complex interaction between cancer cells and the microenvironment plays an essential role in all stages of tumourigenesis. Despite the significance of this interplay, alterations in protein composition underlying tumour-stroma interactions are largely unknown. The aim of this study was to identify stromal proteins with clinical relevance in non-small cell lung cancer (NSCLC). A list encompassing 203 stromal candidate genes was compiled based on gene expression array data and available literature. The protein expression of these genes in human NSCLC was screened using the Human Protein Atlas. Twelve proteins were selected that showed a differential stromal staining pattern (BGN, CD99, DCN, EMILIN1, FBN1, PDGFRB, PDLIM5, POSTN, SPARC, TAGLN, TNC and VCAN). The corresponding antibodies were applied on tissue microarrays, including 190 NSCLC samples, and stromal staining was correlated with clinical parameters. Higher stromal expression of CD99 was associated with better prognosis in the univariate (p = 0.037) and multivariate (p = 0.039) analysis. The association was independent from the proportion of tumour stroma, the fraction of inflammatory cells and clinical and pathological parameters like stage, performance status and tumour histology. The prognostic impact of stromal CD99 protein expression was confirmed in an independent cohort of 240 NSCLC patients (p = 0.008). Furthermore, double-staining confocal fluorescence microscopy showed that CD99 was expressed in stromal lymphocytes as well as in cancer-associated fibroblasts. Based on a comprehensive screening strategy the membrane protein CD99 was identified as a novel stromal factor with clinical relevance. The results support the concept that stromal properties have an important impact on tumour progression.", "doi": "10.1002/ijc.27518", "pmid": "22392539", "labels": {"Array and Analysis Facility": null, "Tissue Profiling": null}, "xrefs": [{"db": "GEO", "description": "Expression profiling by array", "key": "GSE33363"}], "notes": [], "created": "2017-05-04T14:55:51.474Z", "modified": "2018-11-14T11:24:08.142Z"}, {"entity": "publication", "iuid": "167e14d4c9514936905ce24bf6eb8776", "links": {"self": {"href": "https://publications.scilifelab.se/publication/167e14d4c9514936905ce24bf6eb8776.json"}, "display": {"href": "https://publications.scilifelab.se/publication/167e14d4c9514936905ce24bf6eb8776"}}, "title": "Contribution of TMC6 and TMC8 (EVER1 and EVER2) variants to cervical cancer susceptibility.", "authors": [{"family": "Castro", "given": "Felipe A", "initials": "FA"}, {"family": "Ivansson", "given": "Emma L", "initials": "EL"}, {"family": "Schmitt", "given": "Markus", "initials": "M"}, {"family": "Juko-Pecirep", "given": "Ivana", "initials": "I"}, {"family": "Kjellberg", "given": "Lennart", "initials": "L"}, {"family": "Hildesheim", "given": "Allan", "initials": "A"}, {"family": "Gyllensten", "given": "Ulf B", "initials": "UB"}, {"family": "Pawlita", "given": "Michael", "initials": "M"}], "type": "journal article", "published": "2012-01-15", "journal": {"volume": "130", "issn": "1097-0215", "issue": "2", "pages": "349-355", "title": "Int. J. Cancer", "issn-l": "0020-7136"}, "abstract": "Cervical cancer (CxCa) is caused by persistent human papillomavirus (HPV) infection; genetic predisposition is also suspected to play a role. Our study is a targeted candidate gene follow-up based on: (i) strong clinical evidence demonstrating that mutations in the TMC6 and TMC8 (EVER1 and EVER2) genes associate with the HPV-associated disease epidermodysplasia verruciformis (EV) and (ii) recent epidemiological data suggesting a genetic susceptibility conferred by polymorphisms in such genes for skin and CxCa. Clarifying the association of the TMC6/8 genes with risk of CxCa will help in understanding why some HPV-infected women develop persistent infection, cervical lesions and eventually cancer while others do not. Twenty-two single nucleotide polymorphisms (SNPs) harboring the TMC6/8 genes were genotyped in 2,989 cases with cervical intraepithelial neoplasia grade III or invasive CxCa and 2,281 controls from the Swedish population. Association was evaluated in logistic regression models. Two SNPs displayed association with cervical disease: rs2290907 [odds ratio (OR)(GGvsAA) = 0.6, 95% confidence interval (95% CI): 0.3-0.9, p = 0.02)] and rs16970849 (OR(AGvsGG) = 0.8, 95% CI: 0.66-0.98, p = 0.03). The present data support the involvement of the TMC6/8 region in CxCa susceptibility but further analyses are needed to replicate our findings, fully characterize the region and understand the function of the genetic variants involved.", "doi": "10.1002/ijc.26016", "pmid": "21387292", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pmc", "key": "PMC3530613"}, {"db": "mid", "key": "NIHMS428292"}], "notes": [], "created": "2017-05-04T15:02:07.986Z", "modified": "2020-01-21T13:56:00.878Z"}], "created": "2017-05-09T09:12:10.081Z", "modified": "2020-11-27T13:14:01.262Z"}