{"entity": "journal", "iuid": "09ca141009c44efebc79e75856933f8e", "timestamp": "2026-07-22T17:45:21.732Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Eur.%20J.%20Cancer.json"}, "display": {"href": "https://publications.scilifelab.se/journal/Eur.%20J.%20Cancer"}}, "title": "Eur. J. Cancer", "issn": "1879-0852", "issn-l": "0959-8049", "publications_count": 3, "publications": [{"entity": "publication", "iuid": "a10ef57139814fb299f0fd7187b6b2d3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a10ef57139814fb299f0fd7187b6b2d3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a10ef57139814fb299f0fd7187b6b2d3"}}, "title": "FGFR1 overexpression in non-small cell lung cancer is mediated by genetic and epigenetic mechanisms and is a determinant of FGFR1 inhibitor response.", "authors": [{"family": "Bogatyrova", "given": "Olga", "initials": "O"}, {"family": "Mattsson", "given": "Johanna S M", "initials": "JSM", "orcid": "0000-0002-5294-7808", "researcher": {"href": "https://publications.scilifelab.se/researcher/894626ea67fd459eb08e4a9c4768fb09.json"}}, {"family": "Ross", "given": "Edith M", "initials": "EM"}, {"family": "Sanderson", "given": "Michael P", "initials": "MP"}, {"family": "Backman", "given": "Max", "initials": "M"}, {"family": "Botling", "given": "Johan", "initials": "J"}, {"family": "Brunnstr\u00f6m", "given": "Hans", "initials": "H", "orcid": "0000-0001-7402-138X", "researcher": {"href": "https://publications.scilifelab.se/researcher/618b52d539ee4e36ba7f9ce3b23f9d7f.json"}}, {"family": "Kurppa", "given": "Pinja", "initials": "P", "orcid": "0000-0003-3790-3986", "researcher": {"href": "https://publications.scilifelab.se/researcher/4f5b2c06aade428490f10e5eaf015d51.json"}}, {"family": "La Fleur", "given": "Linn\u00e9a", "initials": "L"}, {"family": "Strell", "given": "Carina", "initials": "C", "orcid": "0000-0002-3783-7256", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb77b417ef2b479fb267969c3a557617.json"}}, {"family": "Wilm", "given": "Claudia", "initials": "C"}, {"family": "Zimmermann", "given": "Astrid", "initials": "A"}, {"family": "Esdar", "given": "Christina", "initials": "C"}, {"family": "Micke", "given": "Patrick", "initials": "P", "orcid": "0000-0003-1210-5961", "researcher": {"href": "https://publications.scilifelab.se/researcher/fc0cba74e74a4c39a8f96319cb9a3034.json"}}], "type": "journal article", "published": "2021-07-00", "journal": {"title": "Eur. J. Cancer", "issn": "1879-0852", "volume": "151", "issue": null, "pages": "136-149", "issn-l": "0959-8049"}, "abstract": "Amplification of fibroblast growth factor receptor 1 (FGFR1) in non-small cell lung cancer (NSCLC) has been considered as an actionable drug target. However, pan-FGFR tyrosine kinase inhibitors did not demonstrate convincing clinical efficacy in FGFR1-amplified NSCLC patients. This study aimed to characterise the molecular context of FGFR1 expression and to define biomarkers predictive of FGFR1 inhibitor response. In this study, 635 NSCLC samples were characterised for FGFR1 protein expression by immunohistochemistry and copy number gain (CNG) by in situ hybridisation (n = 298) or DNA microarray (n = 189). FGFR1 gene expression (n = 369) and immune cell profiles (n = 309) were also examined. Furthermore, gene expression, methylation and microRNA data from The Cancer Genome Atlas (TCGA) were compared. A panel of FGFR1-amplified NSCLC patient-derived xenograft (PDX) models were tested for response to the selective FGFR1 antagonist M6123. A minority of patients demonstrated FGFR1 CNG (10.5%) or increased FGFR1 mRNA (8.7%) and protein expression (4.4%). FGFR1 CNG correlated weakly with FGFR1 gene and protein expression. Tumours overexpressing FGFR1 protein were typically devoid of driver alterations (e.g. EGFR, KRAS) and showed reduced infiltration of T-lymphocytes and lower PD-L1 expression. Promoter methylation and microRNA were identified as regulators of FGFR1 expression in NSCLC and other cancers. Finally, NSCLC PDX models demonstrating FGFR1 amplification and FGFR1 protein overexpression were sensitive to M6123. The unique molecular and immune features of tumours with high FGFR1 expression provide a rationale to stratify patients in future clinical trials of FGFR1 pathway-targeting agents.", "doi": "10.1016/j.ejca.2021.04.005", "pmid": "33984662", "labels": {"NGI Stockholm (Genomics Production)": null, "NGI Stockholm (Genomics Applications)": null, "National Genomics Infrastructure": null}, "xrefs": [{"db": "pii", "key": "S0959-8049(21)00226-4"}], "notes": [], "created": "2021-06-09T12:16:54.718Z", "modified": "2021-11-10T12:23:43.669Z"}, {"entity": "publication", "iuid": "ee7cd1df9c4e48c086c61222e6510c86", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ee7cd1df9c4e48c086c61222e6510c86.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ee7cd1df9c4e48c086c61222e6510c86"}}, "title": "An immune gene expression signature distinguishes central nervous system metastases from primary tumours in non-small-cell lung cancer.", "authors": [{"family": "Tsakonas", "given": "Georgios", "initials": "G"}, {"family": "Lewensohn", "given": "Rolf", "initials": "R"}, {"family": "Botling", "given": "Johan", "initials": "J"}, {"family": "Ortiz-Villalon", "given": "Cristian", "initials": "C"}, {"family": "Micke", "given": "Patrick", "initials": "P"}, {"family": "Friesland", "given": "Signe", "initials": "S"}, {"family": "Nord", "given": "Helena", "initials": "H"}, {"family": "Lindskog", "given": "Magnus", "initials": "M"}, {"family": "Sandelin", "given": "Martin", "initials": "M"}, {"family": "Hydbring", "given": "Per", "initials": "P"}, {"family": "Ekman", "given": "Simon", "initials": "S", "orcid": "0000-0002-8343-6226", "researcher": {"href": "https://publications.scilifelab.se/researcher/0fcb2b2956a84f43a7b485573f445ff2.json"}}], "type": "journal article", "published": "2020-06-00", "journal": {"title": "Eur. J. Cancer", "issn": "1879-0852", "volume": "132", "issue": null, "pages": "24-34", "issn-l": "0959-8049"}, "abstract": "Dissemination of non-small-cell lung cancer (NSCLC) in the central nervous system is a frequent and challenging clinical problem. Systemic or local therapies rarely prolong survival and have modest activity regarding local control. Alterations in gene expression in brain metastasis versus primary tumour may increase aggressiveness and impair therapeutic efforts.\n\nWe identified 25 patients with surgically removed NSCLC brain metastases in two different patient cohorts. For 13 of these patients, primary tumour samples were available. Gene expression analysis using the nCounter\u00ae PanCancer Immune Profiling gene expression panel (nanoString technologies Inc.) was performed in brain metastases and primary tumour samples. Identification of differentially expressed genes was conducted on normalized data using the nSolver analysis software.\n\nWe compared gene expression patterns in brain metastases with primary tumours. Brain metastasis samples displayed a distinct clustering pattern compared to primary tumour samples with a statistically significant downregulation of genes related to immune response and immune cell activation. Results from KEGG term analysis on differentially expressed genes revealed a concomitant enrichment of multiple KEGG terms associated with the immune system. We identified a 12-gene immune signature that clearly separated brain metastases from primary tumours.\n\nWe identified a unique gene downregulation pattern in brain metastases compared with primary tumours. This finding may explain the lower intracranial efficacy of systemic therapy, especially immunotherapy, in brain metastasis of patients with NSCLC.", "doi": "10.1016/j.ejca.2020.03.014", "pmid": "32325417", "labels": {"Clinical Genomics Uppsala": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0959-8049(20)30155-6"}], "notes": [], "created": "2020-12-08T15:43:55.833Z", "modified": "2024-01-16T13:48:42.459Z"}, {"entity": "publication", "iuid": "59ec533b78ce498da5e03aa6d32178da", "links": {"self": {"href": "https://publications.scilifelab.se/publication/59ec533b78ce498da5e03aa6d32178da.json"}, "display": {"href": "https://publications.scilifelab.se/publication/59ec533b78ce498da5e03aa6d32178da"}}, "title": "Breast cancer in young women and prognosis: How important are proliferation markers?", "authors": [{"family": "Fredholm", "given": "Hanna", "initials": "H"}, {"family": "Magnusson", "given": "Kristina", "initials": "K"}, {"family": "Lindstr\u00f6m", "given": "Linda S", "initials": "LS"}, {"family": "Tobin", "given": "Nicholas P", "initials": "NP"}, {"family": "Lindman", "given": "Henrik", "initials": "H"}, {"family": "Bergh", "given": "Jonas", "initials": "J"}, {"family": "Holmberg", "given": "Lars", "initials": "L"}, {"family": "Pont\u00e9n", "given": "Fredrik", "initials": "F"}, {"family": "Frisell", "given": "Jan", "initials": "J"}, {"family": "Fredriksson", "given": "Irma", "initials": "I"}], "type": "comparative study", "published": "2017-10-00", "journal": {"title": "Eur. J. Cancer", "issn": "1879-0852", "volume": "84", "issue": null, "pages": "278-289", "issn-l": "0959-8049"}, "abstract": "Compared to middle-aged women, young women with breast cancer have a higher risk of systemic disease. We studied expression of proliferation markers in relation to age and subtype and their association with long-term prognosis.\n\nDistant disease-free survival (DDFS) was studied in 504 women aged <40 years and 383 women aged \u226540 years from a population-based cohort. Information on patient characteristics, treatment and follow-up was collected from medical records. Tissue microarrays were produced for analysis of oestrogen receptor, progesterone receptor (PR), Her2, Ki-67\u00a0and cyclins.\n\nYoung women with luminal tumours had significantly higher expression of Ki-67 and cyclins. Proliferation markers were prognostic only within this subtype. Ki-67 was a prognostic indicator only in young women with luminal PR+ tumours. The optimal cut-off for Ki-67 varied by age. High expression of cyclin E1 conferred a better DDFS in women aged <40 years with luminal PR- tumours (hazard ratio [HR] 0.47 [0.24-0.92]). Age <40 years was an independent risk factor of DDFS exclusively in women with luminal B PR+ tumours (HR 2.35 [1.22-4.50]). Young women with luminal B PR- tumours expressing low cyclin E1 had a six-fold risk of distant disease compared with luminal A (HR 6.21 [2.17-17.6]).\n\nThe higher expression of proliferation markers in young women does not have a strong impact on prognosis. Ki-67 is only prognostic in the subgroup of young women with luminal PR+\u00a0tumours. The only cyclin adding prognostic value beyond subtype is cyclin E1. Age is an independent prognostic factor only in women with luminal B PR+ tumours.", "doi": "10.1016/j.ejca.2017.07.044", "pmid": "28844016", "labels": {"Tissue Profiling": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0959-8049(17)31177-2"}], "notes": [], "created": "2017-11-05T12:43:28.113Z", "modified": "2017-11-05T12:43:28.149Z"}], "created": "2017-11-05T12:43:28.140Z", "modified": "2020-11-27T13:14:07.901Z"}