title: Profiling cancer testis antigens in non-small-cell lung cancer.
abstract: 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.
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Dijana
authors.initials: D
authors.lastname: Djureinovic
authors.affiliation: Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Björn M
authors.initials: BM
authors.lastname: Hallström
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Horie
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Johanna Sofia Margareta
authors.initials: JSM
authors.lastname: Mattsson
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Linnea
authors.initials: L
authors.lastname: La Fleur
authors.affiliation: Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Linn
authors.initials: L
authors.lastname: Fagerberg
authors.affiliation: Department of Pathology, Regional Laboratories Region Skåne, Lund, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Brunnström
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lindskog
authors.affiliation: Department of Statistics, Technical University of Dortmund, Dortmund, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Madjar
authors.affiliation: Department of Statistics, Technical University of Dortmund, Dortmund, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Rahnenführer
authors.affiliation: Department of Radiology, Oncology and Radiation Sciences, Section of Oncology, and.
authors.forename: Simon
authors.initials: S
authors.lastname: Ekman
authors.affiliation: Department of Clinical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ståhle
authors.affiliation: Department of Respiratory Medicine, Centre for Research and Development, Uppsala University, County Council of Gävleborg, Gävle, Sweden.
authors.forename: Hirsh
authors.initials: H
authors.lastname: Koyi
authors.affiliation: Department of Respiratory Medicine, Centre for Research and Development, Uppsala University, County Council of Gävleborg, Gävle, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Brandén
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors, Technical University of Dortmund, Dortmund, Germany.
authors.forename: Karolina
authors.initials: K
authors.lastname: Edlund
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors, Technical University of Dortmund, Dortmund, Germany.
authors.forename: Jan G
authors.initials: JG
authors.lastname: Hengstler
authors.affiliation: Uppsala University Hospital, Regional Cancer Center, Uppsala, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Lambe
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Saito
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Botling
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Pontén
authors.affiliation: Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Mathias
authors.initials: M
authors.lastname: Uhlén
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Patrick
authors.initials: P
authors.lastname: Micke
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D009687:Nuclear Proteins / Q000378:metabolism*; D011379:Prognosis; D017423:Sequence Analysis, RNA; D059467:Transcriptome; D014174:Transketolase / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D009687:Nuclear Proteins; C404411:VCX protein, human; C542434:cancer testis antigen NXF2, human; C505431:TKTL1 protein, human; D014174:Transketolase