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Profiling cancer testis antigens in non-small-cell lung cancer
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
KTH Royal Inst Technol, Sci Life Lab, Stockholm, Sweden..
Univ Tokyo, Grad Sch Med, Dept Resp Med, Tokyo, Japan..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
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2016 (English)In: JCI INSIGHT, ISSN 2379-3708, Vol. 1, no 10, e86837Article in journal (Refereed) Published
Abstract [en]

Cancer testis antigens (CTAs) are of clinical interest as biomarkers and present valuable targets for immunotherapy. To comprehensively characterize the CTA landscape of non-small-cell lung cancer (NSCLC), we compared RNAseq data from 199 NSCLC tissues to the normal transcriptome of 142 samples from 32 different normal organs. Of 232 CTAs currently annotated in the Caner Testis Database (CTdatabase), 96 were confirmed in NSCLC. To obtain an unbiased CTA profile of NSCLC, we applied stringent criteria on our RNAseq data set and defined 90 genes as CTAs, of which 55 genes were not annotated in the CTdatabase, thus representing potential new CTAs. Cluster analysis revealed that CTA expression is histology dependent and concurrent expression is common. IHC confirmed tissue-specific protein expression of selected new CTAs (TKTL1, TGIF2LX, VCX, and CXORF67). Furthermore, methylation was identified as a regulatory mechanism of CTA expression based on independent data from The Cancer Genome Atlas. The proposed prognostic impact of CTAs in lung cancer was not confirmed, neither in our RNAseq cohort nor in an independent meta-analysis of 1,117 NSCLC cases. In summary, we defined a set of 90 reliable CTAs, including information on protein expression, methylation, and survival association. The detailed RNAseq catalog can guide biomarker studies and efforts to identify targets for immunotherapeutic strategies.

Place, publisher, year, edition, pages
2016. Vol. 1, no 10, e86837
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-310039DOI: 10.1172/jci.insight.86837ISI: 000387113300012PubMedID: 27699219OAI: oai:DiVA.org:uu-310039DiVA: diva2:1054821
Available from: 2016-12-09 Created: 2016-12-09 Last updated: 2016-12-09Bibliographically approved

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Djureinovic, DijanaMattsson, Johanna Sofia MargaretaLa Fleur, LinneaLindskog, CeciliaEkman, SimonStåhle, ElisabethKoyi, HirshBrandén, EvaBotling, JohanPontén, FredrikMicke, Patrick
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Department of Immunology, Genetics and PathologyExperimental and Clinical OncologyUCR-Uppsala Clinical Research CenterCentre for Research and Development, GävleborgMolecular tools
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