{"entity": "journal", "iuid": "84d3762b48394373ba857dcf423042bf", "timestamp": "2026-07-14T01:38:19.508Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/BMC%20Cancer.json"}, "display": {"href": "https://publications.scilifelab.se/journal/BMC%20Cancer"}}, "title": "BMC Cancer", "issn": "1471-2407", "issn-l": "1471-2407", "publications_count": 26, "publications": [{"entity": "publication", "iuid": "43a4afd4fd2046b0926cb13af644d8b7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/43a4afd4fd2046b0926cb13af644d8b7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/43a4afd4fd2046b0926cb13af644d8b7"}}, "title": "Metformin inhibits small intestinal neuroendocrine tumor growth in vivo", "authors": [{"family": "Axling", "given": "Fredrik", "initials": "F", "orcid": "0000-0003-3748-3176", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d84ca11d6f2449583a0fa81eaf1e64c.json"}}, {"family": "Backman", "given": "Samuel", "initials": "S"}, {"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": "Barazeghi", "given": "Elham", "initials": "E", "orcid": "0000-0003-2943-0613", "researcher": {"href": "https://publications.scilifelab.se/researcher/d7a017acddb7499185b6917ba7e652f6.json"}}, {"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": "2026-06-25", "journal": {"title": "BMC Cancer", "issn": "1471-2407", "volume": "26", "issue": "1", "issn-l": "1471-2407"}, "abstract": "Small intestinal neuroendocrine tumors (SI-NETs) are slow-growing but highly metastatic, with most patients presenting metastases at diagnosis. Radical surgery remains the only potential curative option when feasible. Consequently, there is a critical need for novel therapeutic strategies that can limit tumor progression and enable more personalized treatment approaches in combination with current clinical practices. In this study, we evaluated the impact of metformin on SI-NET cell growth in vivo, characterized the associated microRNA expression profile, and identified potential driver genes modulated by metformin treatment.\n\nA total of 22 SI-NET xenograft mouse models were established using CNDT2.5 and GOT1 cells. Mice were treated with metformin (2.56 mg/mL in drinking water) or water as control for 4 weeks. To explore the molecular impact of metformin, both small-RNA and total-RNA sequencing were performed on the dissected xenograft tumors. Proliferation and apoptosis were further evaluated by immunohistochemistry.\n\nIn vivo treatment of SI-NET cells with metformin led to a reduction in tumor size in both CNDT2.5 and GOT1 xenograft models. Our sequencing analyses identified seven altered microRNAs and 1,776 differentially expressed genes in metformin-treated tumors compared to controls. To uncover potential driver genes in SI-NETs affected by metformin, we compared the differentially expressed genes from GOT1 xenograft model with those identified by comparing single-cell RNA profile of enterochromaffin cells to SI-NETs. This novel approach revealed a set of significantly regulated genes, including those involved in tumor proliferation, apoptosis, and metastasis, as well as genes related to voltage-gated calcium channels and signal transduction.\n\nOur novel findings support further investigation of metformin as a potential therapeutic agent in clinical trials for SI-NET patients, and suggest that identified miRNAs should be assessed as potential predictive biomarkers for metformin treatment. This study highlights novel candidate driver genes affected by metformin, which are associated with key cellular processes and enterochromaffin cell's function, offering insights into the underlying mechanisms in SI-NETs.", "doi": "10.1186/s12885-026-16418-z", "pmid": "42350991", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "NGI Short read": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12885-026-16418-z"}, {"db": "pmc", "key": "PMC13295228"}], "notes": [], "created": "2026-06-26T12:55:09.115Z", "modified": "2026-06-28T12:30:52.987Z"}, {"entity": "publication", "iuid": "80b726eec6d64bbd8d0aa8c1a36f8959", "links": {"self": {"href": "https://publications.scilifelab.se/publication/80b726eec6d64bbd8d0aa8c1a36f8959.json"}, "display": {"href": "https://publications.scilifelab.se/publication/80b726eec6d64bbd8d0aa8c1a36f8959"}}, "title": "Public and patient involvement: a survey on knowledge, experience and opinions among researchers within a precision oncology European project.", "authors": [{"family": "Mosconi", "given": "Paola", "initials": "P"}, {"family": "Colombo", "given": "Cinzia", "initials": "C"}, {"family": "Paletta", "given": "Pasquale", "initials": "P"}, {"family": "Gangeri", "given": "Laura", "initials": "L"}, {"family": "Pellegrini", "given": "Chiara", "initials": "C"}, {"family": "Garralda", "given": "Elena", "initials": "E"}, {"family": "Miceli", "given": "Rosalba", "initials": "R"}, {"family": "Brunelli", "given": "Cinzia", "initials": "C"}, {"family": "CEE_DART Consortium", "given": "", "initials": ""}], "type": "journal article", "published": "2023-08-30", "journal": {"title": "BMC Cancer", "issn": "1471-2407", "volume": "23", "issue": "1", "pages": "814", "issn-l": "1471-2407"}, "abstract": "Patient and Public Involvement (PPI) is slowly but steadily being implemented in all phases of clinical research. As part of the European project \"Building Data Rich Clinical Trials\" a survey was launched to investigate the knowledge, experiences and opinions on this topic of clinicians and researchers from seven European clinical and non-clinical centers (Cancer Core Europe).\n\nAn invitation to take part in a cross-sectional web survey was sent to 199 clinicians and researchers working in the field of precision oncology. The questionnaire was developed ad hoc because no existing questionnaires met the purpose of this study. The analysis takes account of whether respondents had experience on PPI or not.\n\nOn a total of 101 respondents, this survey reveals that 76.2% of them knew about PPI before answering the questionnaire, 54.5% had experience in the previous five years and 86.1% were interested in a training course on this topic. PPI knowledge grew together with career seniority (peak of 86.5% for established career professionals), while the group most interested in a course was the early-career professionals (100.0%). Finally, the majority of respondents stated they had no training or education on PPI (67.3% of experienced and 82.6% of not-experienced respondents).\n\nThis survey shows that most cancer researchers knew the term PPI, even if only a little more than half of them had any relative experience. Opinions on PPI benefits, negative effects, barriers and requirements differed between the groups of PPI experienced and not-experienced respondents, showing that experience itself can influence respondents' opinions. Most of respondents reported they would prefer a training course based on practical rather than theoretical tools.", "doi": "10.1186/s12885-023-11262-x", "pmid": "37648965", "labels": {"Global Proteomics and Proteogenomics": "Technology development"}, "xrefs": [{"db": "pmc", "key": "PMC10470190"}, {"db": "pii", "key": "10.1186/s12885-023-11262-x"}], "notes": [], "created": "2023-12-03T19:32:35.607Z", "modified": "2023-12-03T19:32:35.611Z"}, {"entity": "publication", "iuid": "ff2c40df55e34e3baf4877363a35b322", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ff2c40df55e34e3baf4877363a35b322.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ff2c40df55e34e3baf4877363a35b322"}}, "title": "Elevated levels of MMP12 sourced from macrophages are associated with poor prognosis in urothelial bladder cancer.", "authors": [{"family": "Kerzeli", "given": "Iliana K", "initials": "IK"}, {"family": "Kostakis", "given": "Alexandros", "initials": "A"}, {"family": "T\u00fcrker", "given": "Polat", "initials": "P"}, {"family": "Malmstr\u00f6m", "given": "Per-Uno", "initials": "PU"}, {"family": "Hemdan", "given": "Tammer", "initials": "T"}, {"family": "Mezheyeuski", "given": "Artur", "initials": "A"}, {"family": "Ward", "given": "Douglas G", "initials": "DG"}, {"family": "Bryan", "given": "Richard T", "initials": "RT"}, {"family": "Segersten", "given": "Ulrika", "initials": "U"}, {"family": "Lord", "given": "Martin", "initials": "M"}, {"family": "Mangsbo", "given": "Sara M", "initials": "SM"}], "type": "journal article", "published": "2023-06-30", "journal": {"title": "BMC Cancer", "issn": "1471-2407", "volume": "23", "issue": "1", "pages": "605", "issn-l": "1471-2407"}, "abstract": "Urothelial bladder cancer is most frequently diagnosed at the non-muscle-invasive stage (NMIBC). However, recurrences and interventions for intermediate and high-risk NMIBC patients impact the quality of life. Biomarkers for patient stratification could help to avoid unnecessary interventions whilst indicating aggressive measures when required.\n\nIn this study, immuno-oncology focused, multiplexed proximity extension assays were utilised to analyse plasma (n = 90) and urine (n = 40) samples from 90 newly-diagnosed and treatment-na\u00efve bladder cancer patients. Public single-cell RNA-sequencing and microarray data from patient tumour tissues and murine OH-BBN-induced urothelial carcinomas were also explored to further corroborate the proteomic findings.\n\nPlasma from muscle-invasive, urothelial bladder cancer patients displayed higher levels of MMP7 (p = 0.028) and CCL23 (p = 0.03) compared to NMIBC patients, whereas urine displayed higher levels of CD27 (p = 0.044) and CD40 (p = 0.04) in the NMIBC group by two-sided Wilcoxon rank-sum tests. Random forest survival and multivariable regression analyses identified increased MMP12 plasma levels as an independent marker (p < 0.001) associated with shorter overall survival (HR = 1.8, p < 0.001, 95% CI:1.3-2.5); this finding was validated in an independent patient OLINK cohort, but could not be established using a transcriptomic microarray dataset. Single-cell transcriptomics analyses indicated tumour-infiltrating macrophages as a putative source of MMP12.\n\nThe measurable levels of tumour-localised, immune-cell-derived MMP12 in blood suggest MMP12 as an important biomarker that could complement histopathology-based risk stratification. As MMP12 stems from infiltrating immune cells rather than the tumor cells themselves, analyses performed on tissue biopsy material risk a biased selection of biomarkers produced by the tumour, while ignoring the surrounding microenvironment.", "doi": "10.1186/s12885-023-11100-0", "pmid": "37391708", "labels": {"Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10311740"}, {"db": "pii", "key": "10.1186/s12885-023-11100-0"}], "notes": [], "created": "2023-11-29T19:27:10.569Z", "modified": "2023-11-29T19:27:10.572Z"}, {"entity": "publication", "iuid": "b5186c1db9354a4494586d06b728006f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b5186c1db9354a4494586d06b728006f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b5186c1db9354a4494586d06b728006f"}}, "title": "Exposure to nonanoic acid alters small intestinal neuroendocrine tumor phenotype.", "authors": [{"family": "Almobarak", "given": "Bilal", "initials": "B"}, {"family": "Amlani", "given": "Vishal", "initials": "V"}, {"family": "Inge", "given": "Linda", "initials": "L"}, {"family": "Hofving", "given": "Tobias", "initials": "T"}, {"family": "Muth", "given": "Andreas", "initials": "A"}, {"family": "Nilsson", "given": "Ola", "initials": "O"}, {"family": "Johansson", "given": "Martin", "initials": "M"}, {"family": "Arvidsson", "given": "Yvonne", "initials": "Y"}, {"family": "Elias", "given": "Erik", "initials": "E"}], "type": "journal article", "published": "2023-03-23", "journal": {"title": "BMC Cancer", "issn": "1471-2407", "volume": "23", "issue": "1", "pages": "267", "issn-l": "1471-2407"}, "abstract": "Small intestinal neuroendocrine tumors (SI-NET) are highly differentiated and genetically stable malignant tumors, yet they often present with advanced metastatic spread at the time of diagnosis. In contrast to many other types of malignant tumors, primary SI-NET are often asymptomatic and typically smaller in size compared to adjacent lymph node metastases. This study explores the hypothesis that stimulating the chemosensing olfactory receptor 51E1 (OR51E1) decreases SI-NET proliferation suggesting a mechanism that explains a difference in proliferative rate based on tumor location.\n\nClinical data was used to address difference in tumor size depending on location. A SI-NET tissue microarray was used to evaluate expression of OR51E1 and olfactory marker protein (OMP). Primary cultured tumor cells from 5 patients were utilized to determine the effect of OR51E1 agonist nonanoic acid on metabolic activity. The SI-NET cell line GOT1 was used to determine effects of nonanoic acid on the transcriptome as well as long-term effects of nonanoic acid exposure with regards to cell proliferation, serotonin secretion, alterations of the cell-cycle and morphology.\n\nTumor size differed significantly based on location. OR51E1 and OMP were generally expressed in SI-NET. Primary SI-NET cells responded to nonanoic acid with a dose dependent altered metabolic activity and this was replicated in the GOT1 cell line but not in the MCF10A control cell line. Nonanoic acid treatment in GOT1 cells upregulated transcripts related to neuroendocrine differentiation and hormone secretion. Long-term nonanoic acid treatment of GOT1 cells decreased proliferation, induced senescence, and altered cell morphology.\n\nOur results raise the possibility that exposure of intraluminal metabolites could represent a mechanism determining aspects of the SI-NET tumor phenotype. However, we could not causally link the observed effects of nonanoic acid exposure to the OR51E1 receptor.", "doi": "10.1186/s12885-023-10722-8", "pmid": "36959559", "labels": {"Clinical Genomics Gothenburg": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10035137"}, {"db": "pii", "key": "10.1186/s12885-023-10722-8"}], "notes": [], "created": "2023-11-30T22:29:33.805Z", "modified": "2023-11-30T22:29:33.810Z"}, {"entity": "publication", "iuid": "3a2ea3833cf745f0a0fceb4c0573a25e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3a2ea3833cf745f0a0fceb4c0573a25e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3a2ea3833cf745f0a0fceb4c0573a25e"}}, "title": "Characterization of surface markers on extracellular vesicles isolated from lymphatic exudate from patients with breast cancer.", "authors": [{"family": "Ekstr\u00f6m", "given": "Karin", "initials": "K"}, {"family": "Crescitelli", "given": "Rossella", "initials": "R"}, {"family": "P\u00e9tursson", "given": "Hafsteinn Ingi", "initials": "HI"}, {"family": "Johansson", "given": "Junko", "initials": "J"}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C"}, {"family": "Olofsson Bagge", "given": "Roger", "initials": "R"}], "type": "journal article", "published": "2022-01-10", "journal": {"title": "BMC Cancer", "issn": "1471-2407", "volume": "22", "issue": "1", "pages": "50", "issn-l": "1471-2407"}, "abstract": "Breast cancer is the most common cancer, and the leading cause of cancer-related deaths, among females world-wide. Recent research suggests that extracellular vesicles (EVs) play a major role in the development of breast cancer metastasis. Axillary lymph node dissection (ALND) is a procedure in patients with known lymph node metastases, and after surgery large amounts of serous fluid are produced from the axilla. The overall aim was to isolate and characterize EVs from axillary serous fluid, and more specifically to determine if potential breast cancer biomarkers could be identified.\n\nLymphatic drain fluid was collected from 7 patients with breast cancer the day after ALND. EVs were isolated using size exclusion chromatography, quantified and detected by nanoparticle tracking analysis, electron microscopy, nano flow cytometry and western blot. The expression of 37 EV surface proteins was evaluated by flow cytometry using the MACSPlex Exosome kit.\n\nLymphatic drainage exudate retrieved after surgery from all 7 patients contained EVs. The isolated EVs were positive for the typical EV markers CD9, CD63, CD81 and Flotillin-1 while albumin was absent, indicating low contamination from blood proteins. In total, 24 different EV surface proteins were detected. Eleven of those proteins were detected in all patients, including the common EV markers CD9, CD63 and CD81, cancer-related markers CD24, CD29, CD44 and CD146, platelet markers CD41b, CD42a and CD62p as well as HLA-DR/DP/DQ. Furthermore, CD29 and CD146 were enriched in Her2+ patients compared to patients with Her2- tumors.\n\nLymphatic drainage exudate retrieved from breast cancer patients after surgery contains EVs that can be isolated using SEC isolation. The EVs have several cancer-related markers including CD24, CD29, CD44 and CD146, proteins of potential interest as biomarkers as well as to increase the understanding of the mechanisms of cancer biology.", "doi": "10.1186/s12885-021-08870-w", "pmid": "35012489", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8744234"}, {"db": "pii", "key": "10.1186/s12885-021-08870-w"}], "notes": [], "created": "2023-02-16T08:23:50.786Z", "modified": "2023-02-16T08:23:50.789Z"}, {"entity": "publication", "iuid": "d3777afc02b2443aa6be5785553e91a5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d3777afc02b2443aa6be5785553e91a5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d3777afc02b2443aa6be5785553e91a5"}}, "title": "SMAD4 haploinsufficiency in small intestinal neuroendocrine tumors.", "authors": [{"family": "Hofving", "given": "Tobias", "initials": "T"}, {"family": "Elias", "given": "Erik", "initials": "E"}, {"family": "Rehammar", "given": "Anna", "initials": "A"}, {"family": "Inge", "given": "Linda", "initials": "L"}, {"family": "Altiparmak", "given": "G\u00fclay", "initials": "G"}, {"family": "Persson", "given": "Marta", "initials": "M"}, {"family": "Kristiansson", "given": "Erik", "initials": "E"}, {"family": "Johansson", "given": "Martin E", "initials": "ME"}, {"family": "Nilsson", "given": "Ola", "initials": "O"}, {"family": "Arvidsson", "given": "Yvonne", "initials": "Y", "orcid": "0000-0002-9599-3791", "researcher": {"href": "https://publications.scilifelab.se/researcher/d3cca2ea2e5d4ef78c6a9beaf517bbc5.json"}}], "type": "journal article", "published": "2021-01-28", "journal": {"title": "BMC Cancer", "issn": "1471-2407", "volume": "21", "issue": "1", "pages": "101", "issn-l": "1471-2407"}, "abstract": "Patients with small intestinal neuroendocrine tumors (SINETs) frequently present with lymph node and liver metastases at the time of diagnosis, but the molecular changes that lead to the progression of these tumors are largely unknown. Sequencing studies have only identified recurrent point mutations at low frequencies with CDKN1B being the most common harboring heterozygous mutations in less than 10% of all tumors. Although SINETs are genetically stable tumors with a low frequency of point mutations and indels, they often harbor recurrent hemizygous copy number alterations (CNAs) yet the functional implications of these CNA are unclear.\n\nUtilizing comparative genomic hybridization (CGH) arrays we analyzed the CNA profile of 131 SINETs from 117 patients. Two tumor suppressor genes and corresponding proteins i.e. SMAD4, and CDKN1B, were further characterized using a tissue microarray (TMA) with 846 SINETs. Immunohistochemistry (IHC) was used to quantify protein expression in TMA samples and this was correlated with chromosome number evaluated with fluorescent in-situ hybridization (FISH). Intestinal tissue from a Smad4+/- mouse model was used to detect entero-endocrine cell hyperplasia with IHC.\n\nAnalyzing the CGH arrays we found loss of chromosome 18q and SMAD4 in 71% of SINETs and that focal loss of chromosome 12 affecting the CDKN1B was present in 9.4% of SINETs. No homozygous loss of chromosome 18 was detected. Hemizygous loss of SMAD4, but not CDKN1B, significantly correlated with reduced protein levels but hemizygous loss of SMAD4 did not induce entero-endocrine cell hyperplasia in the Smad4+/- mouse model. In addition, patients with low SMAD4 protein expression in primary tumors more often presented with metastatic disease.\n\nHemizygous loss of chromosome 18q and the SMAD4 gene is the most common genetic event in SINETs and our results suggests that this could influence SMAD4 protein expression and spread of metastases. Although SMAD4 haploinsufficiency alone did not induce tumor initiation, loss of chromosome 18 could represent an evolutionary advantage in SINETs explaining the high prevalence of this aberration. Functional consequences of reduced SMAD4 protein levels could hypothetically be a potential mechanism as to why loss of chromosome 18 appears to be clonally selected in SINETs.", "doi": "10.1186/s12885-021-07786-9", "pmid": "33509126", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7841913"}, {"db": "pii", "key": "10.1186/s12885-021-07786-9"}], "notes": [], "created": "2023-02-16T08:17:10.434Z", "modified": "2023-02-16T08:17:10.476Z"}, {"entity": "publication", "iuid": "1931acc06b2149ed84e7bb277ac30b26", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1931acc06b2149ed84e7bb277ac30b26.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1931acc06b2149ed84e7bb277ac30b26"}}, "title": "Comprehensive metabolomics analysis of prostate cancer tissue in relation to tumor aggressiveness and TMPRSS2-ERG fusion status.", "authors": [{"family": "Dudka", "given": "Ilona", "initials": "I"}, {"family": "Thysell", "given": "Elin", "initials": "E"}, {"family": "Lundquist", "given": "Kristina", "initials": "K"}, {"family": "Antti", "given": "Henrik", "initials": "H"}, {"family": "Iglesias-Gato", "given": "Diego", "initials": "D"}, {"family": "Flores-Morales", "given": "Amilcar", "initials": "A"}, {"family": "Bergh", "given": "Anders", "initials": "A"}, {"family": "Wikstr\u00f6m", "given": "Pernilla", "initials": "P"}, {"family": "Gr\u00f6bner", "given": "Gerhard", "initials": "G", "orcid": "0000-0001-7380-8797", "researcher": {"href": "https://publications.scilifelab.se/researcher/85bd86ebc85d4653bc880bc9be25bc80.json"}}], "type": "journal article", "published": "2020-05-18", "journal": {"title": "BMC Cancer", "issn": "1471-2407", "volume": "20", "issue": "1", "pages": "437", "issn-l": "1471-2407"}, "abstract": "Prostate cancer (PC) can display very heterogeneous phenotypes ranging from indolent asymptomatic to aggressive lethal forms. Understanding how these PC subtypes vary in their striving for energy and anabolic molecules is of fundamental importance for developing more effective therapies and diagnostics. Here, we carried out an extensive analysis of prostate tissue samples to reveal metabolic alterations during PC development and disease progression and furthermore between TMPRSS2-ERG rearrangement-positive and -negative PC subclasses.\n\nComprehensive metabolomics analysis of prostate tissue samples was performed by non-destructive high-resolution magic angle spinning nuclear magnetic resonance (1H HR MAS NMR). Subsequently, samples underwent moderate extraction, leaving tissue morphology intact for histopathological characterization. Metabolites in tissue extracts were identified by 1H/31P NMR and liquid chromatography-mass spectrometry (LC-MS). These metabolomics profiles were analyzed by chemometric tools and the outcome was further validated using proteomic data from a separate sample cohort.\n\nThe obtained metabolite patterns significantly differed between PC and benign tissue and between samples with high and low Gleason score (GS). Five key metabolites (phosphocholine, glutamate, hypoxanthine, arginine and \u03b1-glucose) were identified, who were sufficient to differentiate between cancer and benign tissue and between high to low GS. In ERG-positive PC, the analysis revealed several acylcarnitines among the increased metabolites together with decreased levels of proteins involved in \u03b2-oxidation; indicating decreased acyl-CoAs oxidation in ERG-positive tumors. The ERG-positive group also showed increased levels of metabolites and proteins involved in purine catabolism; a potential sign of increased DNA damage and oxidative stress.\n\nOur comprehensive metabolomic analysis strongly indicates that ERG-positive PC and ERG-negative PC should be considered as different subtypes of PC; a fact requiring different, sub-type specific treatment strategies for affected patients.", "doi": "10.1186/s12885-020-06908-z", "pmid": "32423389", "labels": {"Swedish Metabolomics Centre": "Service", "Swedish NMR Centre": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1186/s12885-020-06908-z"}, {"db": "pmc", "key": "PMC7236196"}], "notes": [], "created": "2020-11-24T20:28:48.037Z", "modified": "2025-10-17T13:03:56.902Z"}, {"entity": "publication", "iuid": "448bba4069fc46a7b03d5fe9b2771693", "links": {"self": {"href": "https://publications.scilifelab.se/publication/448bba4069fc46a7b03d5fe9b2771693.json"}, "display": {"href": "https://publications.scilifelab.se/publication/448bba4069fc46a7b03d5fe9b2771693"}}, "title": "Multiplex plasma protein profiling identifies novel markers to discriminate patients with adenocarcinoma of the lung.", "authors": [{"family": "Djureinovic", "given": "Dijana", "initials": "D", "orcid": "0000-0002-1852-5409", "researcher": {"href": "https://publications.scilifelab.se/researcher/17058abc202c4da794e35722c1f234df.json"}}, {"family": "Pont\u00e9n", "given": "Victor", "initials": "V"}, {"family": "Landelius", "given": "Per", "initials": "P"}, {"family": "Al Sayegh", "given": "Sahar", "initials": "S"}, {"family": "Kappert", "given": "Kai", "initials": "K"}, {"family": "Kamali-Moghaddam", "given": "Masood", "initials": "M", "orcid": "0000-0002-1303-2218", "researcher": {"href": "https://publications.scilifelab.se/researcher/290dd535fb414c68bc49a8a2b7995770.json"}}, {"family": "Micke", "given": "Patrick", "initials": "P"}, {"family": "St\u00e5hle", "given": "Elisabeth", "initials": "E"}], "type": "journal article", "published": "2019-07-29", "journal": {"volume": "19", "issn": "1471-2407", "issue": "1", "pages": "741", "title": "BMC Cancer", "issn-l": "1471-2407"}, "abstract": "The overall prognosis of non-small cell lung cancer (NSCLC) is poor, and currently only patients with localized disease are potentially curable. Therefore, preferably non-invasively determined biomarkers that detect NSCLC patients at early stages of the disease are of high clinical relevance. The aim of this study was to identify and validate novel protein markers in plasma using the highly sensitive DNA-assisted multiplex proximity extension assay (PEA) to discriminate NSCLC from other lung diseases.\n\nPlasma samples were collected from a total of 343 patients who underwent surgical resection for different lung diseases, including 144 patients with lung adenocarcinoma (LAC), 68 patients with non-malignant lung disease, 83 patients with lung metastasis of colorectal cancers and 48 patients with typical carcinoid. One microliter of plasma was analyzed using PEA, allowing detection and quantification of 92 established cancer related proteins. The concentrations of the plasma proteins were compared between disease groups.\n\nThe comparison between LAC and benign samples revealed significantly different plasma levels for four proteins; CXCL17, CEACAM5, VEGFR2 and ERBB3 (adjusted p-value < 0.05). A multi-parameter classifier was developed to discriminate between samples from LAC patients and from patients with non-malignant lung conditions. With a bootstrap aggregated decision tree algorithm (TreeBagger), a sensitivity of 93% and specificity of 64% was achieved to detect LAC in this risk population.\n\nBy applying the highly sensitive PEA, reliable protein profiles could be determined in microliter amounts of plasma. We further identified proteins that demonstrated different plasma concentration in defined disease groups and developed a signature that holds potential to be included in a screening assay for early lung cancer detection.", "doi": "10.1186/s12885-019-5943-3", "pmid": "31357969", "labels": {"Clinical Biomarkers": "Service", "PLA and Single Cell Proteomics": "Collaborative", "Affinity Proteomics Uppsala": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12885-019-5943-3"}, {"db": "pmc", "key": "PMC6664554"}], "notes": [], "created": "2020-01-07T15:01:06.242Z", "modified": "2024-01-16T13:48:44.077Z"}, {"entity": "publication", "iuid": "dde25453f5ee4c1ba51cd47bd3b3ba3c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/dde25453f5ee4c1ba51cd47bd3b3ba3c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/dde25453f5ee4c1ba51cd47bd3b3ba3c"}}, "title": "A novel human in vitro papillomavirus type 16 positive tonsil cancer cell line with high sensitivity to radiation and cisplatin.", "authors": [{"family": "Forslund", "given": "Ola", "initials": "O"}, {"family": "Sugiyama", "given": "Natsuki", "initials": "N"}, {"family": "Wu", "given": "Chengjun", "initials": "C"}, {"family": "Ravi", "given": "Naveen", "initials": "N"}, {"family": "Jin", "given": "Yuesheng", "initials": "Y"}, {"family": "Swoboda", "given": "Sabine", "initials": "S"}, {"family": "Andersson", "given": "Fredrik", "initials": "F"}, {"family": "Bzhalava", "given": "Davit", "initials": "D"}, {"family": "Hultin", "given": "Emilie", "initials": "E"}, {"family": "Paulsson", "given": "Kajsa", "initials": "K"}, {"family": "Dillner", "given": "Joakim", "initials": "J"}, {"family": "Schwartz", "given": "Stefan", "initials": "S"}, {"family": "Wennerberg", "given": "Johan", "initials": "J"}, {"family": "Ekblad", "given": "Lars", "initials": "L"}], "type": "journal article", "published": "2019-03-25", "journal": {"volume": "19", "issn": "1471-2407", "issue": "1", "pages": "265", "title": "BMC Cancer", "issn-l": "1471-2407"}, "abstract": "Human papillomavirus (HPV) is an established risk factor for oropharyngeal squamous cell carcinoma (OSCC). The aim was to establish cell lines from HPV-positive tonsil carcinomas to be used for treatment development.\n\nFresh samples from 23 HPV-positive tonsil carcinomas were cultivated in vitro. The established cell line was analyzed for viral characteristics, cell karyotype, TP53 status, and growth capabilities in nude mice. In vitro studies of sensitivities to radiation, cisplatin and cetuximab were performed.\n\nAfter 19\u2009months (eight passages), one cell line, LU-HNSCC-26, was established in vitro and also grew as xenografts. The tumor was from a 48\u2009year old non-smoking man with non-keratinizing, p16 positive tonsil OSCC, stage T2N0M0 with HPV16. It contained 19.5 (CV% 3.7) HPV16 copies/cell (passage 8). The complete HPV16 genome sequence was obtained. Episomal HPV16 was present with an E2/E7 ratio of 1.1 (CV% 2.6). In addition, HPV16 mRNA specific for the intact E2 gene was detected. The viral expression manifested 1.0 (CV% 0.1) E7 mRNA copies per HPV16 genome. The karyotype was determined and the cell line demonstrated wild type TP53. The ID50 for radiation was 0.90\u2009Gy and the IC50 for cisplatin was 0.99\u2009\u03bcmol/L. The cell line was inhibited to a maximum of 18% by cetuximab.\n\nWe established an in vitro tonsil carcinoma cell line containing episomal HPV16. This is an important step towards efficient treatment development.", "doi": "10.1186/s12885-019-5469-8", "pmid": "30909875", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12885-019-5469-8"}, {"db": "pmc", "key": "PMC6434888"}], "notes": [], "created": "2019-04-10T09:40:28.753Z", "modified": "2020-01-21T13:56:13.922Z"}, {"entity": "publication", "iuid": "b365c625896c416cb51dd5c3cd8d52d8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b365c625896c416cb51dd5c3cd8d52d8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b365c625896c416cb51dd5c3cd8d52d8"}}, "title": "Metabolic control of PPAR activity by aldehyde dehydrogenase regulates invasive cell behavior and predicts survival in hepatocellular and renal clear cell carcinoma.", "authors": [{"family": "Andrejeva", "given": "Diana", "initials": "D"}, {"family": "Kugler", "given": "Jan-Michael", "initials": "JM"}, {"family": "Nguyen", "given": "Hung Thanh", "initials": "HT"}, {"family": "Malmendal", "given": "Anders", "initials": "A"}, {"family": "Holm", "given": "Mette Lind", "initials": "ML"}, {"family": "Toft", "given": "Birgitte Groenkaer", "initials": "BG"}, {"family": "Loya", "given": "Anand C", "initials": "AC"}, {"family": "Cohen", "given": "Stephen M", "initials": "SM", "orcid": "0000-0003-2858-9163", "researcher": {"href": "https://publications.scilifelab.se/researcher/6d04ca4ed117442d9b691937a739ff5b.json"}}], "type": "journal article", "published": "2018-11-28", "journal": {"title": "BMC Cancer", "issn": "1471-2407", "volume": "18", "issue": "1", "pages": "1180", "issn-l": "1471-2407"}, "abstract": "Changes in cellular metabolism are now recognized as potential drivers of cancer development, rather than as secondary consequences of disease. Here, we explore the mechanism by which metabolic changes dependent on aldehyde dehydrogenase impact cancer development.\n\nALDH7A1 was identified as a potential cancer gene using a Drosophila in vivo metastasis model. The role of the human ortholog was examined using RNA interference in cell-based assays of cell migration and invasion. 1H-NMR metabolite profiling was used to identify metabolic changes in ALDH7A1-depleted cells. Publically available cancer gene expression data was interrogated to identify a gene-expression signature associated with depletion of ALDH7A1. Computational pathway and gene set enrichment analysis was used to identify signaling pathways and cellular processes that were correlated with reduced ALDH7A1 expression in cancer. A variety of statistical tests used to evaluate these analyses are described in detail in the methods section. Immunohistochemistry was used to assess ALDH7A1 expression in tissue samples from cancer patients.\n\nDepletion of ALDH7A1 increased cellular migration and invasiveness in vitro. Depletion of ALDH7A1 led to reduced levels of metabolites identified as ligands for Peroxisome proliferator-activated receptor (PPAR\u03b1). Analysis of publically available cancer gene expression data revealed that ALDH7A1 mRNA levels were reduced in many human cancers, and that this correlated with poor survival in kidney and liver cancer patients. Using pathway and gene set enrichment analysis, we establish a correlation between low ALDH7A1 levels, reduced PPAR signaling and reduced patient survival. Metabolic profiling showed that endogenous PPAR\u03b1 ligands were reduced in ALDH7A1-depleted cells. ALDH7A1-depletion led to reduced PPAR transcriptional activity. Treatment with a PPAR\u03b1 agonist restored normal cellular behavior. Low ALDH7A1 protein levels correlated with poor clinical outcome in hepatocellular and renal clear cell carcinoma patients.\n\nWe provide evidence that low ALDH7A1 expression is a useful prognostic marker of poor clinical outcome for hepatocellular and renal clear cell carcinomas and hypothesize that patients with low ALDH7A1 might benefit from therapeutic approaches addressing PPAR\u03b1 activity.", "doi": "10.1186/s12885-018-5061-7", "pmid": "30486822", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12885-018-5061-7"}, {"db": "pmc", "key": "PMC6264057"}], "notes": [], "created": "2019-01-10T10:12:48.259Z", "modified": "2025-10-17T13:03:58.443Z"}, {"entity": "publication", "iuid": "dcdd0e77f81742ba8bd8593d8b5a6659", "links": {"self": {"href": "https://publications.scilifelab.se/publication/dcdd0e77f81742ba8bd8593d8b5a6659.json"}, "display": {"href": "https://publications.scilifelab.se/publication/dcdd0e77f81742ba8bd8593d8b5a6659"}}, "title": "Intra-tumor heterogeneity in breast cancer has limited impact on transcriptomic-based molecular profiling.", "authors": [{"family": "Karthik", "given": "Govindasamy-Muralidharan", "initials": "GM"}, {"family": "Rantalainen", "given": "Mattias", "initials": "M"}, {"family": "St\u00e5lhammar", "given": "Gustav", "initials": "G"}, {"family": "L\u00f6vrot", "given": "John", "initials": "J"}, {"family": "Ullah", "given": "Ikram", "initials": "I"}, {"family": "Alkodsi", "given": "Amjad", "initials": "A"}, {"family": "Ma", "given": "Ran", "initials": "R"}, {"family": "Wedlund", "given": "Lena", "initials": "L"}, {"family": "Lindberg", "given": "Johan", "initials": "J"}, {"family": "Frisell", "given": "Jan", "initials": "J"}, {"family": "Bergh", "given": "Jonas", "initials": "J"}, {"family": "Hartman", "given": "Johan", "initials": "J"}], "type": "journal article", "published": "2017-11-29", "journal": {"volume": "17", "issn": "1471-2407", "issue": "1", "pages": "802", "title": "BMC Cancer", "issn-l": "1471-2407"}, "abstract": "Transcriptomic profiling of breast tumors provides opportunity for subtyping and molecular-based patient stratification. In diagnostic applications the specimen profiled should be representative of the expression profile of the whole tumor and ideally capture properties of the most aggressive part of the tumor. However, breast cancers commonly exhibit intra-tumor heterogeneity at molecular, genomic and in phenotypic level, which can arise during tumor evolution. Currently it is not established to what extent a random sampling approach may influence molecular breast cancer diagnostics.\n\nIn this study we applied RNA-sequencing to quantify gene expression in 43 pieces (2-5 pieces per tumor) from 12 breast tumors (Cohort 1). We determined molecular subtype and transcriptomic grade for all tumor pieces and analysed to what extent pieces originating from the same tumors are concordant or discordant with each other. Additionally, we validated our finding in an independent cohort consisting of 19 pieces (2-6 pieces per tumor) from 6 breast tumors (Cohort 2) profiled using microarray technique. Exome sequencing was also performed on this cohort, to investigate the extent of intra-tumor genomic heterogeneity versus the intra-tumor molecular subtype classifications.\n\nMolecular subtyping was consistent in 11 out of 12 tumors and transcriptomic grade assignments were consistent in 11 out of 12 tumors as well. Molecular subtype predictions revealed consistent subtypes in four out of six patients in this cohort 2. Interestingly, we observed extensive intra-tumor genomic heterogeneity in these tumor pieces but not in their molecular subtype classifications.\n\nOur results suggest that macroscopic intra-tumoral transcriptomic heterogeneity is limited and unlikely to have an impact on molecular diagnostics for most patients.", "doi": "10.1186/s12885-017-3815-2", "pmid": "29187174", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12885-017-3815-2"}, {"db": "pmc", "key": "PMC5708109"}], "notes": [], "created": "2018-01-10T09:45:04.700Z", "modified": "2020-01-21T13:56:11.065Z"}, {"entity": "publication", "iuid": "d1e74ad1e3134682be2aa625c2c3d42f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d1e74ad1e3134682be2aa625c2c3d42f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d1e74ad1e3134682be2aa625c2c3d42f"}}, "title": "Tartrate-resistant acid phosphatase (TRAP/ACP5) promotes metastasis-related properties via TGF\u03b22/T\u03b2R and CD44 in MDA-MB-231 breast cancer cells.", "authors": [{"family": "Reithmeier", "given": "Anja", "initials": "A"}, {"family": "Panizza", "given": "Elena", "initials": "E"}, {"family": "Krumpel", "given": "Michael", "initials": "M"}, {"family": "Orre", "given": "Lukas M", "initials": "LM"}, {"family": "Branca", "given": "Rui M M", "initials": "RMM"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Ek-Rylander", "given": "Barbro", "initials": "B"}, {"family": "Andersson", "given": "G\u00f6ran", "initials": "G"}], "type": "journal article", "published": "2017-09-15", "journal": {"volume": "17", "issn": "1471-2407", "issue": "1", "pages": "650", "title": "BMC Cancer", "issn-l": "1471-2407"}, "abstract": "Tartrate-resistant acid phosphatase (TRAP/ACP5), a metalloenzyme that is characteristic for its expression in activated osteoclasts and in macrophages, has recently gained considerable focus as a driver of metastasis and was associated with clinically relevant parameters of cancer progression and cancer aggressiveness.\n\nMDA-MB-231 breast cancer cells with different TRAP expression levels (overexpression and knockdown) were generated and characterized for protein expression and activity levels. Functional cell experiments, such as proliferation, migration and invasion assays were performed as well as global phosphoproteomic and proteomic analysis was conducted to connect molecular perturbations to the phenotypic changes.\n\nWe identified an association between metastasis-related properties of TRAP-overexpressing MDA-MB-231 breast cancer cells and a TRAP-dependent regulation of Transforming growth factor (TGF\u03b2) pathway proteins and Cluster of differentiation 44 (CD44). Overexpression of TRAP increased anchorage-independent and anchorage-dependent cell growth and proliferation, induced a more elongated cellular morphology and promoted cell migration and invasion. Migration was increased in the presence of the extracellular matrix (ECM) proteins osteopontin and fibronectin and the basement membrane proteins collagen IV and laminin I. TRAP-induced properties were reverted upon shRNA-mediated knockdown of TRAP or treatment with the small molecule TRAP inhibitor 5-PNA. Global phosphoproteomics and proteomics analyses identified possible substrates of TRAP phosphatase activity or signaling intermediates and outlined a TRAP-dependent regulation of proteins involved in cell adhesion and ECM organization. Upregulation of TGF\u03b2 isoform 2 (TGF\u03b22), TGF\u03b2 receptor type 1 (T\u03b2R1) and Mothers against decapentaplegic homolog 2 (SMAD2), as well as increased intracellular phosphorylation of CD44 were identified upon TRAP perturbation. Functional antibody-mediated blocking and chemical inhibition demonstrated that TRAP-dependent migration and proliferation is regulated via TGF\u03b22/T\u03b2R, whereas proliferation beyond basal levels is regulated through CD44.\n\nAltogether, TRAP promotes metastasis-related cell properties in MDA-MB-231 breast cancer cells via TGF\u03b22/T\u03b2R and CD44, thereby identifying a potential signaling mechanism associated to TRAP action in breast cancer cells.", "doi": "10.1186/s12885-017-3616-7", "pmid": "28915803", "labels": {"Clinical Proteomics Mass spectrometry": "Service", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12885-017-3616-7"}, {"db": "pmc", "key": "PMC5602878"}], "notes": [], "created": "2017-12-05T16:14:25.657Z", "modified": "2021-07-08T11:36:15.281Z"}, {"entity": "publication", "iuid": "486b9a2053714ec0b814295e77d2e76d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/486b9a2053714ec0b814295e77d2e76d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/486b9a2053714ec0b814295e77d2e76d"}}, "title": "Loss of DIP2C in RKO cells stimulates changes in DNA methylation and epithelial-mesenchymal transition.", "authors": [{"family": "Larsson", "given": "Chatarina", "initials": "C"}, {"family": "Ali", "given": "Muhammad Akhtar", "initials": "MA"}, {"family": "Pandzic", "given": "Tatjana", "initials": "T"}, {"family": "Lindroth", "given": "Anders M", "initials": "AM"}, {"family": "He", "given": "Liqun", "initials": "L"}, {"family": "Sj\u00f6blom", "given": "Tobias", "initials": "T"}], "type": "journal article", "published": "2017-07-17", "journal": {"volume": "17", "issn": "1471-2407", "issue": "1", "pages": "487", "title": "BMC Cancer", "issn-l": "1471-2407"}, "abstract": "The disco-interacting protein 2 homolog C (DIP2C) gene is an uncharacterized gene found mutated in a subset of breast and lung cancers. To understand the role of DIP2C in tumour development we studied the gene in human cancer cells.\n\nWe engineered human DIP2C knockout cells by genome editing in cancer cells. The growth properties of the engineered cells were characterised and transcriptome and methylation analyses were carried out to identify pathways deregulated by inactivation of DIP2C. Effects on cell death pathways and epithelial-mesenchymal transition traits were studied based on the results from expression profiling.\n\nKnockout of DIP2C in RKO cells resulted in cell enlargement and growth retardation. Expression profiling revealed 780 genes for which the expression level was affected by the loss of DIP2C, including the tumour-suppressor encoding CDKN2A gene, the epithelial-mesenchymal transition (EMT) regulator-encoding ZEB1, and CD44 and CD24 that encode breast cancer stem cell markers. Analysis of DNA methylation showed more than 30,000 sites affected by differential methylation, the majority of which were hypomethylated following loss of DIP2C. Changes in DNA methylation at promoter regions were strongly correlated to changes in gene expression, and genes involved with EMT and cell death were enriched among the differentially regulated genes. The DIP2C knockout cells had higher wound closing capacity and showed an increase in the proportion of cells positive for cellular senescence markers.\n\nLoss of DIP2C triggers substantial DNA methylation and gene expression changes, cellular senescence and epithelial-mesenchymal transition in cancer cells.", "doi": "10.1186/s12885-017-3472-5", "pmid": "28716088", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12885-017-3472-5"}, {"db": "pmc", "key": "PMC5513093"}], "notes": [], "created": "2017-10-17T09:31:57.476Z", "modified": "2024-01-16T13:48:47.742Z"}, {"entity": "publication", "iuid": "d696eb5a55e8441fa0660644f896cd63", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d696eb5a55e8441fa0660644f896cd63.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d696eb5a55e8441fa0660644f896cd63"}}, "title": "A systematic search strategy identifies cubilin as independent prognostic marker for renal cell carcinoma.", "authors": [{"family": "Gremel", "given": "Gabriela", "initials": "G"}, {"family": "Djureinovic", "given": "Dijana", "initials": "D"}, {"family": "Niinivirta", "given": "Marjut", "initials": "M"}, {"family": "Laird", "given": "Alexander", "initials": "A"}, {"family": "Ljungqvist", "given": "Oscar", "initials": "O"}, {"family": "Johannesson", "given": "Henrik", "initials": "H"}, {"family": "Bergman", "given": "Julia", "initials": "J"}, {"family": "Edqvist", "given": "Per-Henrik", "initials": "PH"}, {"family": "Navani", "given": "Sanjay", "initials": "S"}, {"family": "Khan", "given": "Naila", "initials": "N"}, {"family": "Patil", "given": "Tushar", "initials": "T"}, {"family": "Sivertsson", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}, {"family": "Harrison", "given": "David J", "initials": "DJ"}, {"family": "Ullenhag", "given": "Gustav J", "initials": "GJ"}, {"family": "Stewart", "given": "Grant D", "initials": "GD"}, {"family": "Pont\u00e9n", "given": "Fredrik", "initials": "F"}], "type": "journal article", "published": "2017-01-04", "journal": {"title": "BMC Cancer", "issn": "1471-2407", "volume": "17", "issue": "1", "pages": "9", "issn-l": "1471-2407"}, "abstract": "There is an unmet clinical need for better prognostic and diagnostic tools for renal cell carcinoma (RCC).\n\nHuman Protein Atlas data resources, including the transcriptomes and proteomes of normal and malignant human tissues, were searched for RCC-specific proteins and cubilin (CUBN) identified as a candidate. Patient tissue representing various cancer types was constructed into a tissue microarray (n = 940) and immunohistochemistry used to investigate the specificity of CUBN expression in RCC as compared to other cancers. Two independent RCC cohorts (n = 181; n = 114) were analyzed to further establish the sensitivity of CUBN as RCC-specific marker and to explore if the fraction of RCCs lacking CUBN expression could predict differences in patient survival.\n\nCUBN was identified as highly RCC-specific protein with 58% of all primary RCCs staining positive for CUBN using immunohistochemistry. In venous tumor thrombi and metastatic lesions, the frequency of CUBN expression was increasingly lost. Clear cell RCC (ccRCC) patients with CUBN positive tumors had a significantly better prognosis compared to patients with CUBN negative tumors, independent of T-stage, Fuhrman grade and nodal status (HR 0.382, CI 0.203-0.719, P = 0.003).\n\nCUBN expression is highly specific to RCC and loss of the protein is significantly and independently associated with poor prognosis. CUBN expression in ccRCC provides a promising positive prognostic indicator for patients with ccRCC. The high specificity of CUBN expression in RCC also suggests a role as a new diagnostic marker in clinical cancer differential diagnostics to confirm or rule out RCC.", "doi": "10.1186/s12885-016-3030-6", "pmid": "28052770", "labels": {"Tissue Profiling": "Technology development"}, "xrefs": [{"db": "pii", "key": "10.1186/s12885-016-3030-6"}, {"db": "pmc", "key": "PMC5215231"}], "notes": [], "created": "2017-11-05T12:38:11.316Z", "modified": "2021-07-08T13:44:33.674Z"}, {"entity": "publication", "iuid": "508c656babda482a96344a438394dbd5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/508c656babda482a96344a438394dbd5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/508c656babda482a96344a438394dbd5"}}, "title": "ANLN is a prognostic biomarker independent of Ki-67 and essential for cell cycle progression in primary breast cancer.", "authors": [{"family": "Magnusson", "given": "Kristina", "initials": "K"}, {"family": "Gremel", "given": "Gabriela", "initials": "G"}, {"family": "Ryd\u00e9n", "given": "Lisa", "initials": "L"}, {"family": "Pont\u00e9n", "given": "Victor", "initials": "V"}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}, {"family": "Dimberg", "given": "Anna", "initials": "A"}, {"family": "Jirstr\u00f6m", "given": "Karin", "initials": "K"}, {"family": "Pont\u00e9n", "given": "Fredrik", "initials": "F"}], "type": "journal article", "published": "2016-11-18", "journal": {"volume": "16", "issn": "1471-2407", "issue": "1", "pages": "904", "title": "BMC Cancer", "issn-l": "1471-2407"}, "abstract": "Anillin (ANLN), an actin-binding protein required for cytokinesis, has recently been presented as part of a prognostic marker panel in breast cancer. The objective of the current study was to further explore the prognostic and functional value of ANLN as a single biomarker in breast cancer.\n\nImmunohistochemical assessment of ANLN protein expression was performed in two well characterized breast cancer cohorts (n = 484) with long-term clinical follow-up data and the results were further validated at the mRNA level in a publicly available transcriptomics dataset. The functional relevance of ANLN was investigated in two breast cancer cell lines using RNA interference.\n\nHigh nuclear fraction of ANLN in breast tumor cells was significantly associated with large tumor size, high histological grade, high proliferation rate, hormone receptor negative tumors and poor prognosis in both examined cohorts. Multivariable analysis showed that the association between ANLN and survival was significantly independent of age in cohort I and significantly independent of proliferation, as assessed by Ki-67 expression in tumor cells, age, tumor size, ER and PR status, HER2 status and nodal status in cohort II. Analysis of ANLN mRNA expression confirmed that high expression of ANLN was significantly correlated to poor overall survival in breast cancer patients. Consistent with the role of ANLN during cytokinesis, transient knock-down of ANLN protein expression in breast cancer cell lines resulted in an increase of senescent cells and an accumulation of cells in the G2/M phase of the cell cycle with altered cell morphology including large, poly-nucleated cells. Moreover, ANLN siRNA knockdown also resulted in decreased expression of cyclins D1, A2 and B1.\n\nANLN expression in breast cancer cells plays an important role during cell division and a high fraction of nuclear ANLN expression in tumor cells is correlated to poor prognosis in breast cancer patients, independent of Ki-67, tumor size, hormone receptor status, HER2 status, nodal status and age.", "doi": "10.1186/s12885-016-2923-8", "pmid": "27863473", "labels": {"Tissue Profiling": "Technology development"}, "xrefs": [{"db": "pii", "key": "10.1186/s12885-016-2923-8"}, {"db": "pmc", "key": "PMC5116155"}], "notes": [], "created": "2017-05-03T12:59:20.815Z", "modified": "2021-07-08T13:44:33.234Z"}, {"entity": "publication", "iuid": "c387d19556d54ef98ffde6978e848c04", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c387d19556d54ef98ffde6978e848c04.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c387d19556d54ef98ffde6978e848c04"}}, "title": "Inconsistent results in the analysis of ALK rearrangements in non-small cell lung cancer.", "authors": [{"family": "Mattsson", "given": "Johanna S M", "initials": "JS"}, {"family": "Brunnstr\u00f6m", "given": "Hans", "initials": "H"}, {"family": "Jabs", "given": "Verena", "initials": "V"}, {"family": "Edlund", "given": "Karolina", "initials": "K"}, {"family": "Jirstr\u00f6m", "given": "Karin", "initials": "K"}, {"family": "Mindus", "given": "Stephanie", "initials": "S"}, {"family": "la Fleur", "given": "Linn\u00e9a", "initials": "L"}, {"family": "Pont\u00e9n", "given": "Fredrik", "initials": "F"}, {"family": "Karlsson", "given": "Mats G", "initials": "MG"}, {"family": "Karlsson", "given": "Christina", "initials": "C"}, {"family": "Koyi", "given": "Hirsh", "initials": "H"}, {"family": "Brand\u00e9n", "given": "Eva", "initials": "E"}, {"family": "Botling", "given": "Johan", "initials": "J"}, {"family": "Helenius", "given": "Gisela", "initials": "G", "orcid": "0000-0003-2317-5738", "researcher": {"href": "https://publications.scilifelab.se/researcher/2994acfdacff45ceb9c6b29aae2148c7.json"}}, {"family": "Micke", "given": "Patrick", "initials": "P"}, {"family": "Svensson", "given": "Maria A", "initials": "MA"}], "type": "journal article", "published": "2016-08-05", "journal": {"volume": "16", "issn": "1471-2407", "issue": null, "pages": "603", "title": "BMC Cancer", "issn-l": "1471-2407"}, "abstract": "Identification of targetable EML4-ALK fusion proteins has revolutionized the treatment of a minor subgroup of non-small cell lung cancer (NSCLC) patients. Although fluorescence in situ hybridization (FISH) is regarded as the gold standard for detection of ALK rearrangements, ALK immunohistochemistry (IHC) is often used as screening tool in clinical practice. In order to unbiasedly analyze the diagnostic impact of such a screening strategy, we compared ALK IHC with ALK FISH in three large representative Swedish NSCLC cohorts incorporating clinical parameters and gene expression data.\n\nALK rearrangements were detected using FISH on tissue microarrays (TMAs), including tissue from 851 NSCLC patients. In parallel, ALK protein expression was detected using IHC, applying the antibody clone D5F3 with two different protocols (the FDA approved Ventana CDx assay and our in house Dako IHC protocol). Gene expression microarray data (Affymetrix) was available for 194 patients.\n\nALK rearrangements were detected in 1.7 % in the complete cohort and 2.0 % in the non-squamous cell carcinoma subgroup. ALK protein expression was observed in 1.8 and 1.4 % when applying the Ventana assay or the in house Dako protocol, respectively. The specificity and accuracy of IHC was high (> 98 %), while the sensitivity was between 69 % (Ventana) and 62 % (in house Dako protocol). Furthermore, only 67 % of the ALK IHC positive cases were positive with both IHC assays. Gene expression analysis revealed that 6/194 (3 %) tumors showed high ALK gene expression (\u2265 6 AU) and of them only three were positive by either FISH or IHC.\n\nThe overall frequency of ALK rearrangements based on FISH was lower than previously reported. The sensitivity of both IHC assays was low, and the concordance between the FISH and the IHC assays poor, questioning current strategies to screen with IHC prior to FISH or completely replace FISH by IHC.", "doi": "10.1186/s12885-016-2646-x", "pmid": "27495736", "labels": {"Tissue Profiling": "Collaborative", "Clinical Genomics Uppsala": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC4974795"}, {"db": "pii", "key": "10.1186/s12885-016-2646-x"}], "notes": [], "created": "2017-05-08T07:56:22.206Z", "modified": "2022-11-28T12:40:00.345Z"}, {"entity": "publication", "iuid": "9e58d31bf76440078c7df0a0541e34f0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9e58d31bf76440078c7df0a0541e34f0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9e58d31bf76440078c7df0a0541e34f0"}}, "title": "Microsatellite instability and mutations in BRAF and KRAS are significant predictors of disseminated disease in colon cancer.", "authors": [{"family": "Birgisson", "given": "Helgi", "initials": "H"}, {"family": "Edlund", "given": "Karolina", "initials": "K"}, {"family": "Wallin", "given": "Ulrik", "initials": "U"}, {"family": "P\u00e5hlman", "given": "Lars", "initials": "L"}, {"family": "Kultima", "given": "Hanna G\u00f6ransson", "initials": "HG"}, {"family": "Mayrhofer", "given": "Markus", "initials": "M"}, {"family": "Micke", "given": "Patrick", "initials": "P"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}, {"family": "Botling", "given": "Johan", "initials": "J"}, {"family": "Glimelius", "given": "Bengt", "initials": "B"}, {"family": "Sundstr\u00f6m", "given": "Magnus", "initials": "M"}], "type": "journal article", "published": "2015-03-14", "journal": {"volume": "15", "issn": "1471-2407", "issue": null, "pages": "125", "title": "BMC Cancer", "issn-l": "1471-2407"}, "abstract": "Molecular alterations are well studied in colon cancer, however there is still need for an improved understanding of their prognostic impact. This study aims to characterize colon cancer with regard to KRAS, BRAF, and PIK3CA mutations, microsatellite instability (MSI), and average DNA copy number, in connection with tumour dissemination and recurrence in patients with colon cancer.\n\nDisease stage II-IV colon cancer patients (n\u2009=\u2009121) were selected. KRAS, BRAF, and PIK3CA mutation status was assessed by pyrosequencing and MSI was determined by analysis of mononucleotide repeat markers. Genome-wide average DNA copy number and allelic imbalance was evaluated by SNP array analysis.\n\nPatients with mutated KRAS were more likely to experience disease dissemination (OR 2.75; 95% CI 1.28-6.04), whereas the opposite was observed for patients with BRAF mutation (OR 0.34; 95% 0.14-0.81) or MSI (OR 0.24; 95% 0.09-0.64). Also in the subset of patients with stage II-III disease, both MSI (OR 0.29; 95% 0.10-0.86) and BRAF mutation (OR 0.32; 95% 0.16-0.91) were related to lower risk of distant recurrence. However, average DNA copy number and PIK3CA mutations were not associated with disease dissemination.\n\nThe present study revealed that tumour dissemination is less likely to occur in colon cancer patients with MSI and BRAF mutation, whereas the presence of a KRAS mutation increases the likelihood of disseminated disease.", "doi": "10.1186/s12885-015-1144-x", "pmid": "25884297", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "10.1186/s12885-015-1144-x"}, {"db": "pmc", "key": "PMC4364587"}, {"db": "GEO", "description": "SNP array data", "key": "GSE62875"}], "notes": [], "created": "2017-05-02T12:56:37.304Z", "modified": "2018-11-14T13:42:09.141Z"}, {"entity": "publication", "iuid": "db289820b92841799c82714a754ba549", "links": {"self": {"href": "https://publications.scilifelab.se/publication/db289820b92841799c82714a754ba549.json"}, "display": {"href": "https://publications.scilifelab.se/publication/db289820b92841799c82714a754ba549"}}, "title": "Clonal distribution of BCR-ABL1 mutations and splice isoforms by single-molecule long-read RNA sequencing.", "authors": [{"family": "Cavelier", "given": "Lucia", "initials": "L", "orcid": "0009-0003-8195-370X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f01226edb140436da0c9d166c1f5fe51.json"}}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "H\u00e4ggqvist", "given": "Susana", "initials": "S"}, {"family": "H\u00f6ijer", "given": "Ida", "initials": "I"}, {"family": "Cahill", "given": "Nicola", "initials": "N"}, {"family": "Olsson-Str\u00f6mberg", "given": "Ulla", "initials": "U"}, {"family": "Hermanson", "given": "Monica", "initials": "M"}], "type": "journal article", "published": "2015-02-12", "journal": {"volume": "15", "issn": "1471-2407", "issue": null, "pages": "45", "title": "BMC Cancer", "issn-l": "1471-2407"}, "abstract": "The evolution of mutations in the BCR-ABL1 fusion gene transcript renders CML patients resistant to tyrosine kinase inhibitor (TKI) based therapy. Thus screening for BCR-ABL1 mutations is recommended particularly in patients experiencing poor response to treatment. Herein we describe a novel approach for the detection and surveillance of BCR-ABL1 mutations in CML patients.\n\nTo detect mutations in the BCR-ABL1 transcript we developed an assay based on the Pacific Biosciences (PacBio) sequencing technology, which allows for single-molecule long-read sequencing of BCR-ABL1 fusion transcript molecules. Samples from six patients with poor response to therapy were analyzed both at diagnosis and follow-up. cDNA was generated from total RNA and a 1,6 kb fragment encompassing the BCR-ABL1 transcript was amplified using long range PCR. To estimate the sensitivity of the assay, a serial dilution experiment was performed.\n\nOver 10,000 full-length BCR-ABL1 sequences were obtained for all samples studied. Through the serial dilution analysis, mutations in CML patient samples could be detected down to a level of at least 1%. Notably, the assay was determined to be sufficiently sensitive even in patients harboring a low abundance of BCR-ABL1 levels. The PacBio sequencing successfully identified all mutations seen by standard methods. Importantly, we identified several mutations that escaped detection by the clinical routine analysis. Resistance mutations were found in all but one of the patients. Due to the long reads afforded by PacBio sequencing, compound mutations present in the same molecule were readily distinguished from independent alterations arising in different molecules. Moreover, several transcript isoforms of the BCR-ABL1 transcript were identified in two of the CML patients. Finally, our assay allowed for a quick turn around time allowing samples to be reported upon within 2 days.\n\nIn summary the PacBio sequencing assay can be applied to detect BCR-ABL1 resistance mutations in both diagnostic and follow-up CML patient samples using a simple protocol applicable to routine diagnosis. The method besides its sensitivity, gives a complete view of the clonal distribution of mutations, which is of importance when making therapy decisions.", "doi": "10.1186/s12885-015-1046-y", "pmid": "25880391", "labels": {"National Genomics Infrastructure": "Service", "Clinical Genomics Uppsala": null, "NGI Uppsala (Uppsala Genome Center)": "Service", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": null}, "xrefs": [{"db": "pii", "key": "10.1186/s12885-015-1046-y"}, {"db": "pmc", "key": "PMC4335374"}], "notes": [], "created": "2017-05-02T12:56:42.927Z", "modified": "2024-01-16T13:48:50.802Z"}, {"entity": "publication", "iuid": "f5db7e7b9d0c40f58af9b4f98e7caba3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f5db7e7b9d0c40f58af9b4f98e7caba3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f5db7e7b9d0c40f58af9b4f98e7caba3"}}, "title": "1p36 deletion is a marker for tumour dissemination in microsatellite stable stage II-III colon cancer.", "authors": [{"family": "Mayrhofer", "given": "Markus", "initials": "M"}, {"family": "Kultima", "given": "Hanna G\u00f6ransson", "initials": "HG"}, {"family": "Birgisson", "given": "Helgi", "initials": "H"}, {"family": "Sundstr\u00f6m", "given": "Magnus", "initials": "M"}, {"family": "Mathot", "given": "Lucy", "initials": "L"}, {"family": "Edlund", "given": "Karolina", "initials": "K"}, {"family": "Viklund", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Sj\u00f6blom", "given": "Tobias", "initials": "T"}, {"family": "Botling", "given": "Johan", "initials": "J"}, {"family": "Micke", "given": "Patrick", "initials": "P"}, {"family": "P\u00e5hlman", "given": "Lars", "initials": "L"}, {"family": "Glimelius", "given": "Bengt", "initials": "B"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}], "type": "journal article", "published": "2014-11-24", "journal": {"volume": "14", "issn": "1471-2407", "issue": null, "pages": "872", "title": "BMC Cancer", "issn-l": "1471-2407"}, "abstract": "The clinical behaviour of colon cancer is heterogeneous. Five-year overall survival is 50-65% with all stages included. Recurring somatic chromosomal alterations have been identified and some have shown potential as markers for dissemination of the tumour, which is responsible for most colon cancer deaths. We investigated 115 selected stage II-IV primary colon cancers for associations between chromosomal alterations and tumour dissemination.\n\nFollow-up was at least 5 years for stage II-III patients without distant recurrence. Affymetrix SNP 6.0 microarrays and allele-specific copy number analysis were used to identify chromosomal alterations. Fisher's exact test was used to associate alterations with tumour dissemination, detected at diagnosis (stage IV) or later as recurrent disease (stage II-III).\n\nLoss of 1p36.11-21 was associated with tumour dissemination in microsatellite stable tumours of stage II-IV (odds ratio\u2009=\u20095.5). It was enriched to a similar extent in tumours with distant recurrence within stage II and stage III subgroups, and may therefore be used as a prognostic marker at diagnosis. Loss of 1p36.11-21 relative to average copy number of the genome showed similar prognostic value compared to absolute loss of copies. Therefore, the use of relative loss as a prognostic marker would benefit more patients by applying also to hyperploid cancer genomes. The association with tumour dissemination was supported by independent data from the The Cancer Genome Atlas.\n\nDeletions on 1p36 may be used to guide adjuvant treatment decisions in microsatellite stable colon cancer of stages II and III.", "doi": "10.1186/1471-2407-14-872", "pmid": "25420937", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "1471-2407-14-872"}, {"db": "pmc", "key": "PMC4251789"}], "notes": [], "created": "2017-05-04T15:03:02.416Z", "modified": "2017-05-30T14:50:06.726Z"}, {"entity": "publication", "iuid": "0e20e0d7feff4aa7b671b663a7065744", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0e20e0d7feff4aa7b671b663a7065744.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0e20e0d7feff4aa7b671b663a7065744"}}, "title": "Tyrosine phosphorylation profiling via in situ proximity ligation assay.", "authors": [{"family": "Elfineh", "given": "Lioudmila", "initials": "L"}, {"family": "Classon", "given": "Christina", "initials": "C"}, {"family": "Asplund", "given": "Anna", "initials": "A"}, {"family": "Pettersson", "given": "Ulf", "initials": "U"}, {"family": "Kamali-Moghaddam", "given": "Masood", "initials": "M", "orcid": "0000-0002-1303-2218", "researcher": {"href": "https://publications.scilifelab.se/researcher/290dd535fb414c68bc49a8a2b7995770.json"}}, {"family": "Lind", "given": "Sara Bergstr\u00f6m", "initials": "SB"}], "type": "journal article", "published": "2014-06-13", "journal": {"volume": "14", "issn": "1471-2407", "issue": null, "pages": "435", "title": "BMC Cancer", "issn-l": "1471-2407"}, "abstract": "Tyrosine phosphorylation (pTyr) is an important cancer relevant posttranslational modification since it regulates protein activity and cellular localization. By controlling cell growth and differentiation it plays an important role in tumor development. This paper describes a novel approach for detection and visualization of a panel of pTyr proteins in tumors using in situ proximity ligation assay.\n\nK562 leukemia cells were treated with tyrosine kinase and/or phosphatase inhibitors to induce differences in pTyr levels and mimic cells with different malignant properties. Cells were then probed with one antibody against the pTyr modification and another probe against the detected protein, resulting in a detectable fluorescent signal once the probes were in proximity.\n\nTotal and protein specific pTyr levels on ABL, SHC, ERK2 and PI3K proteins were detected and samples of control and treated cells were distinguished at the pTyr level using this novel approach. Promising results were also detected for formalin fixed and paraffin embedded cells in the micro array format.\n\nThis application of in situ proximity ligation assay is valuable in order to study the pTyr modification of a panel of proteins in large data sets to validate mass spectrometric data and to be combined with tissue microarrays. The approach offers new opportunities to reveal the pTyr signatures in cells of different malignant properties that can be used as biomarker of disease in the future.", "doi": "10.1186/1471-2407-14-435", "pmid": "24928687", "labels": {"PLA and Single Cell Proteomics": "", "Affinity Proteomics Uppsala": "Technology development"}, "xrefs": [{"db": "pii", "key": "1471-2407-14-435"}, {"db": "pmc", "key": "PMC4072613"}], "notes": [], "created": "2017-05-04T14:55:27.663Z", "modified": "2023-04-14T13:56:27.691Z"}, {"entity": "publication", "iuid": "15185a5ef0034f8ea1dcde6ce36c2c01", "links": {"self": {"href": "https://publications.scilifelab.se/publication/15185a5ef0034f8ea1dcde6ce36c2c01.json"}, "display": {"href": "https://publications.scilifelab.se/publication/15185a5ef0034f8ea1dcde6ce36c2c01"}}, "title": "Age dependence of tumor genetics in unfavorable neuroblastoma: arrayCGH profiles of 34 consecutive cases, using a Swedish 25-year neuroblastoma cohort for validation.", "authors": [{"family": "Cetinkaya", "given": "Cihan", "initials": "C"}, {"family": "Martinsson", "given": "Tommy", "initials": "T"}, {"family": "Sandgren", "given": "Johanna", "initials": "J"}, {"family": "Tr\u00e4ger", "given": "Catarina", "initials": "C"}, {"family": "Kogner", "given": "Per", "initials": "P"}, {"family": "Dumanski", "given": "Jan", "initials": "J"}, {"family": "D\u00edaz de St\u00e5hl", "given": "Teresita", "initials": "T"}, {"family": "Hedborg", "given": "Fredrik", "initials": "F"}], "type": "journal article", "published": "2013-05-09", "journal": {"volume": "13", "issn": "1471-2407", "issue": null, "pages": "231", "title": "BMC Cancer", "issn-l": "1471-2407"}, "abstract": "Aggressive neuroblastoma remains a significant cause of childhood cancer death despite current intensive multimodal treatment protocols. The purpose of the present work was to characterize the genetic and clinical diversity of such tumors by high resolution arrayCGH profiling.\n\nBased on a 32K BAC whole-genome tiling path array and using 50-250K Affymetrix SNP array platforms for verification, DNA copy number profiles were generated for 34 consecutive high-risk or lethal outcome neuroblastomas. In addition, age and MYCN amplification (MNA) status were retrieved for 112 unfavorable neuroblastomas of the Swedish Childhood Cancer Registry, representing a 25-year neuroblastoma cohort of Sweden, here used for validation of the findings. Statistical tests used were: Fisher's exact test, Bayes moderated t-test, independent samples t-test, and correlation analysis.\n\nMNA or segmental 11q loss (11q-) was found in 28/34 tumors. With two exceptions, these aberrations were mutually exclusive. Children with MNA tumors were diagnosed at significantly younger ages than those with 11q- tumors (mean: 27.4 vs. 69.5 months; p=0.008; n=14/12), and MNA tumors had significantly fewer segmental chromosomal aberrations (mean: 5.5 vs. 12.0; p<0.001). Furthermore, in the 11q- tumor group a positive correlation was seen between the number of segmental aberrations and the age at diagnosis (Pearson Correlation 0.606; p=0.037). Among nonMNA/non11q- tumors (n=6), one tumor displayed amplicons on 11q and 12q and three others bore evidence of progression from low-risk tumors due to retrospective evidence of disease six years before diagnosis, or due to tumor profiles with high proportions of numerical chromosomal aberrations. An early age at diagnosis of MNA neuroblastomas was verified by registry data, with an average of 29.2 months for 43 cases that were not included in the present study.\n\nMNA and segmental 11q loss define two major genetic variants of unfavorable neuroblastoma with apparent differences in their pace of tumor evolution and in genomic integrity. Other possible, but less common, routes in the development of aggressive tumors are progression of low-risk infant-type lesions, and gene amplifications other than MYCN. Knowledge on such nosological diversity of aggressive neuroblastoma might influence future strategies for therapy.", "doi": "10.1186/1471-2407-13-231", "pmid": "23656755", "labels": {"National Genomics Infrastructure": null, "NGI Stockholm (Genomics Applications)": null, "NGI Stockholm (Genomics Production)": null}, "xrefs": [{"db": "pii", "key": "1471-2407-13-231"}, {"db": "pmc", "key": "PMC3664071"}], "notes": [], "created": "2017-05-04T14:57:49.386Z", "modified": "2020-01-21T13:56:00.846Z"}, {"entity": "publication", "iuid": "588bcc002c0247a2b0dd46872c4c105b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/588bcc002c0247a2b0dd46872c4c105b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/588bcc002c0247a2b0dd46872c4c105b"}}, "title": "Systematic antibody generation and validation via tissue microarray technology leading to identification of a novel protein prognostic panel in breast cancer.", "authors": [{"family": "O Leary", "given": "Patrick C", "initials": "PC"}, {"family": "Penny", "given": "Sarah A", "initials": "SA"}, {"family": "Dolan", "given": "Roisin T", "initials": "RT"}, {"family": "Kelly", "given": "Catherine M", "initials": "CM"}, {"family": "Madden", "given": "Stephen F", "initials": "SF"}, {"family": "Rexhepaj", "given": "Elton", "initials": "E"}, {"family": "Brennan", "given": "Donal J", "initials": "DJ"}, {"family": "McCann", "given": "Amanda H", "initials": "AH"}, {"family": "Pont\u00e9n", "given": "Fredrik", "initials": "F"}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}, {"family": "Zagozdzon", "given": "Radoslaw", "initials": "R"}, {"family": "Duffy", "given": "Michael J", "initials": "MJ"}, {"family": "Kell", "given": "Malcolm R", "initials": "MR"}, {"family": "Jirstr\u00f6m", "given": "Karin", "initials": "K"}, {"family": "Gallagher", "given": "William M", "initials": "WM"}], "type": "journal article", "published": "2013-04-02", "journal": {"volume": "13", "issn": "1471-2407", "issue": null, "pages": "175", "title": "BMC Cancer", "issn-l": "1471-2407"}, "abstract": "Although omic-based discovery approaches can provide powerful tools for biomarker identification, several reservations have been raised regarding the clinical applicability of gene expression studies, such as their prohibitive cost. However, the limited availability of antibodies is a key barrier to the development of a lower cost alternative, namely a discrete collection of immunohistochemistry (IHC)-based biomarkers. The aim of this study was to use a systematic approach to generate and screen affinity-purified, mono-specific antibodies targeting progression-related biomarkers, with a view towards developing a clinically applicable IHC-based prognostic biomarker panel for breast cancer.\n\nWe examined both in-house and publicly available breast cancer DNA microarray datasets relating to invasion and metastasis, thus identifying a cohort of candidate progression-associated biomarkers. Of these, 18 antibodies were released for extended analysis. Validated antibodies were screened against a tissue microarray (TMA) constructed from a cohort of consecutive breast cancer cases (n\u2009=\u2009512) to test the immunohistochemical surrogate signature.\n\nAntibody screening revealed 3 candidate prognostic markers: the cell cycle regulator, Anillin (ANLN); the mitogen-activated protein kinase, PDZ-Binding Kinase (PBK); and the estrogen response gene, PDZ-Domain Containing 1 (PDZK1). Increased expression of ANLN and PBK was associated with poor prognosis, whilst increased expression of PDZK1 was associated with good prognosis. A 3-marker signature comprised of high PBK, high ANLN and low PDZK1 expression was associated with decreased recurrence-free survival (p\u2009<\u20090.001) and breast cancer-specific survival (BCSS) (p\u2009<\u20090.001). This novel signature was associated with high tumour grade (p\u2009<\u20090.001), positive nodal status (p\u2009=\u20090.029), ER-negativity (p\u2009=\u20090.006), Her2-positivity (p\u2009=\u20090.036) and high Ki67 status (p\u2009<\u20090.001). However, multivariate Cox regression demonstrated that the signature was not a significant predictor of BCSS (HR\u2009=\u20096.38; 95% CI\u2009=\u20090.79-51.26, p\u2009=\u20090.082).\n\nWe have developed a comprehensive biomarker pathway that extends from discovery through to validation on a TMA platform. This proof-of-concept study has resulted in the identification of a novel 3-protein prognostic panel. Additional biochemical markers, interrogated using this high-throughput platform, may further augment the prognostic accuracy of this panel to a point that may allow implementation into routine clinical practice.", "doi": "10.1186/1471-2407-13-175", "pmid": "23547718", "labels": {"Tissue Profiling": null}, "xrefs": [{"db": "pii", "key": "1471-2407-13-175"}, {"db": "pmc", "key": "PMC3668187"}], "notes": [], "created": "2017-05-04T14:55:55.320Z", "modified": "2021-07-08T13:44:33.279Z"}, {"entity": "publication", "iuid": "71c62030cc0446d5b86aff2877a1836b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/71c62030cc0446d5b86aff2877a1836b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/71c62030cc0446d5b86aff2877a1836b"}}, "title": "Loss-of-heterozygosity on chromosome 19q in early-stage serous ovarian cancer is associated with recurrent disease.", "authors": [{"family": "Skirnisdottir", "given": "Ingiridur", "initials": "I"}, {"family": "Mayrhofer", "given": "Markus", "initials": "M"}, {"family": "Ryd\u00e5ker", "given": "Maria", "initials": "M"}, {"family": "Akerud", "given": "Helena", "initials": "H"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}], "type": "journal article", "published": "2012-09-12", "journal": {"volume": "12", "issn": "1471-2407", "issue": null, "pages": "407", "title": "BMC Cancer", "issn-l": "1471-2407"}, "abstract": "Ovarian cancer is a heterogeneous disease and prognosis for apparently similar cases of ovarian cancer varies. Recurrence of the disease in early stage (FIGO-stages I-II) serous ovarian cancer results in survival that is comparable to those with recurrent advanced-stage disease. The aim of this study was to investigate if there are specific genomic aberrations that may explain recurrence and clinical outcome.\n\nFifty-one women with early stage serous ovarian cancer were included in the study. DNA was extracted from formalin fixed samples containing tumor cells from ovarian tumors. Tumor samples from thirty-seven patients were analysed for allele-specific copy numbers using OncoScan single nucleotide polymorphism arrays from Affymetrix and the bioinformatic tool Tumor Aberration Prediction Suite. Genomic gains, losses, and loss-of-heterozygosity that associated with recurrent disease were identified.\n\nThe most significant differences (p\u2009<\u20090.01) in Loss-of-heterozygosity (LOH) were identified in two relatively small regions of chromosome 19; 8.0-8,8\u2009Mbp (19 genes) and 51.5-53.0\u2009Mbp (37 genes). Thus, 56 genes on chromosome 19 were potential candidate genes associated with clinical outcome. LOH at 19q (51-56\u2009Mbp) was associated with shorter disease-free survival and was an independent prognostic factor for survival in a multivariate Cox regression analysis. In particular LOH on chromosome 19q (51-56\u2009Mbp) was significantly (p\u2009<\u20090.01) associated with loss of TP53 function.\n\nThe results of our study indicate that presence of two aberrations in TP53 on 17p and LOH on 19q in early stage serous ovarian cancer is associated with recurrent disease. Further studies related to the findings of chromosomes 17 and 19 are needed to elucidate the molecular mechanism behind the recurring genomic aberrations and the poor clinical outcome.", "doi": "10.1186/1471-2407-12-407", "pmid": "22967087", "labels": {"Array and Analysis Facility": null}, "xrefs": [{"db": "pii", "key": "1471-2407-12-407"}, {"db": "pmc", "key": "PMC3495882"}], "notes": [], "created": "2017-05-04T15:02:55.178Z", "modified": "2017-05-30T14:49:43.224Z"}, {"entity": "publication", "iuid": "2206ea195bdb4024815aa4e0581e3f73", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2206ea195bdb4024815aa4e0581e3f73.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2206ea195bdb4024815aa4e0581e3f73"}}, "title": "The presence of tumor associated macrophages in tumor stroma as a prognostic marker for breast cancer patients.", "authors": [{"family": "Medrek", "given": "Catharina", "initials": "C"}, {"family": "Pont\u00e9n", "given": "Fredrik", "initials": "F"}, {"family": "Jirstr\u00f6m", "given": "Karin", "initials": "K"}, {"family": "Leandersson", "given": "Karin", "initials": "K"}], "type": "journal article", "published": "2012-07-23", "journal": {"volume": "12", "issn": "1471-2407", "issue": null, "pages": "306", "title": "BMC Cancer", "issn-l": "1471-2407"}, "abstract": "Tumor associated macrophages (TAMs) are alternatively activated macrophages that enhance tumor progression by promoting tumor cell invasion, migration and angiogenesis. TAMs have an anti-inflammatory function resembling M2 macrophages. CD163 is regarded as a highly specific monocyte/macrophage marker for M2 macrophages. In this study we evaluated the specificity of using the M2 macrophage marker CD163 as a TAM marker and compared its prognostic value with the more frequently used pan-macrophage marker CD68. We also analyzed the prognostic value of the localization of CD163(+) and CD68(+) myeloid cells in human breast cancer.\n\nThe extent of infiltrating CD163(+) or CD68(+) myeloid cells in tumor nest versus tumor stroma was evaluated by immunohistochemistry in tissue microarrays with tumors from 144 breast cancer cases. Spearman's Rho and \u03c7(2) tests were used to examine the correlations between CD163(+) or CD68(+) myeloid cells and clinicopathological parameters. Kaplan Meier analysis and Cox proportional hazards modeling were used to assess the impact of CD163(+) and CD68(+) myeloid cells in tumor stroma and tumor nest, respectively, on recurrence free survival, breast cancer specific and overall survival.\n\nWe found that infiltration of CD163(+) and CD68(+) macrophages into tumor stroma, but not into tumor nest, were of clinical relevance. CD163(+) macrophages in tumor stroma positively correlated with higher grade, larger tumor size, Ki67 positivity, estrogen receptor negativity, progesterone receptor negativity, triple-negative/basal-like breast cancer and inversely correlated with luminal A breast cancer. Some CD163(+) areas lacked CD68 expression, suggesting that CD163 could be used as a general anti-inflammatory myeloid marker with prognostic impact. CD68(+) macrophages in tumor stroma positively correlated to tumor size and inversely correlated to luminal A breast cancer. More importantly, CD68 in tumor stroma was an independent prognostic factor for reduced breast cancer specific survival.\n\nThese findings highlight the importance of analyzing the localization rather than merely the presence of TAMs as a prognostic marker for breast cancer patients.", "doi": "10.1186/1471-2407-12-306", "pmid": "22824040", "labels": {"Tissue Profiling": null}, "xrefs": [{"db": "pii", "key": "1471-2407-12-306"}, {"db": "pmc", "key": "PMC3414782"}], "notes": [], "created": "2017-05-04T14:55:49.746Z", "modified": "2017-05-30T14:54:43.506Z"}, {"entity": "publication", "iuid": "63edf630527848e0b6ac076a603afb2a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/63edf630527848e0b6ac076a603afb2a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/63edf630527848e0b6ac076a603afb2a"}}, "title": "Identification of epigenetically regulated genes that predict patient outcome in neuroblastoma.", "authors": [{"family": "Car\u00e9n", "given": "Helena", "initials": "H"}, {"family": "Djos", "given": "Anna", "initials": "A"}, {"family": "Nethander", "given": "Maria", "initials": "M"}, {"family": "Sj\u00f6berg", "given": "Rose-Marie", "initials": "RM", "orcid": "0000-0003-1363-5796", "researcher": {"href": "https://publications.scilifelab.se/researcher/d08326da26da422ab445a26563843e79.json"}}, {"family": "Kogner", "given": "Per", "initials": "P"}, {"family": "Enstr\u00f6m", "given": "Camilla", "initials": "C"}, {"family": "Nilsson", "given": "Staffan", "initials": "S"}, {"family": "Martinsson", "given": "Tommy", "initials": "T"}], "type": "journal article", "published": "2011-02-11", "journal": {"volume": "11", "issn": "1471-2407", "issue": null, "pages": "66", "title": "BMC Cancer", "issn-l": "1471-2407"}, "abstract": "Epigenetic mechanisms such as DNA methylation and histone modifications are important regulators of gene expression and are frequently involved in silencing tumor suppressor genes.\n\nIn order to identify genes that are epigenetically regulated in neuroblastoma tumors, we treated four neuroblastoma cell lines with the demethylating agent 5-Aza-2'-deoxycytidine (5-Aza-dC) either separately or in conjunction with the histone deacetylase inhibitor trichostatin A (TSA). Expression was analyzed using whole-genome expression arrays to identify genes activated by the treatment. These data were then combined with data from genome-wide DNA methylation arrays to identify candidate genes silenced in neuroblastoma due to DNA methylation.\n\nWe present eight genes (KRT19, PRKCDBP, SCNN1A, POU2F2, TGFBI, COL1A2, DHRS3 and DUSP23) that are methylated in neuroblastoma, most of them not previously reported as such, some of which also distinguish between biological subsets of neuroblastoma tumors. Differential methylation was observed for the genes SCNN1A (p < 0.001), PRKCDBP (p < 0.001) and KRT19 (p < 0.01). Among these, the mRNA expression of KRT19 and PRKCDBP was significantly lower in patients that have died from the disease compared with patients with no evidence of disease (fold change -8.3, p = 0.01 for KRT19 and fold change -2.4, p = 0.04 for PRKCDBP).\n\nIn our study, a low methylation frequency of SCNN1A, PRKCDBP and KRT19 is significantly associated with favorable outcome in neuroblastoma. It is likely that analysis of specific DNA methylation will be one of several methods in future patient therapy stratification protocols for treatment of childhood neuroblastomas.", "doi": "10.1186/1471-2407-11-66", "pmid": "21314941", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (SNP&SEQ Technology Platform)": null}, "xrefs": [{"db": "pii", "key": "1471-2407-11-66"}, {"db": "pmc", "key": "PMC3045360"}], "notes": [], "created": "2017-05-04T15:00:40.779Z", "modified": "2021-07-07T15:55:21.173Z"}, {"entity": "publication", "iuid": "429804ab762c412ca8c87002ab2edf17", "links": {"self": {"href": "https://publications.scilifelab.se/publication/429804ab762c412ca8c87002ab2edf17.json"}, "display": {"href": "https://publications.scilifelab.se/publication/429804ab762c412ca8c87002ab2edf17"}}, "title": "Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer.", "authors": [{"family": "Brennan", "given": "Donal J", "initials": "DJ"}, {"family": "Br\u00e4ndstedt", "given": "Jenny", "initials": "J"}, {"family": "Rexhepaj", "given": "Elton", "initials": "E"}, {"family": "Foley", "given": "Michael", "initials": "M"}, {"family": "Pont\u00e9n", "given": "Fredrik", "initials": "F"}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}, {"family": "Gallagher", "given": "William M", "initials": "WM"}, {"family": "O'Connor", "given": "Darran P", "initials": "DP"}, {"family": "O'Herlihy", "given": "Colm", "initials": "C"}, {"family": "Jirstrom", "given": "Karin", "initials": "K"}], "type": "journal article", "published": "2010-04-01", "journal": {"volume": "10", "issn": "1471-2407", "issue": null, "pages": "125", "title": "BMC Cancer", "issn-l": "1471-2407"}, "abstract": "Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer.\n\nHMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS).\n\nSeventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade.\n\nHMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens.", "doi": "10.1186/1471-2407-10-125", "pmid": "20359358", "labels": {"Tissue Profiling": null}, "xrefs": [{"db": "pii", "key": "1471-2407-10-125"}, {"db": "pmc", "key": "PMC3087316"}], "notes": [], "created": "2017-05-04T14:55:42.475Z", "modified": "2021-07-08T13:44:33.190Z"}], "created": "2017-05-09T09:12:54.653Z", "modified": "2020-11-27T13:14:03.707Z"}