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Profiling cancer testis antigens in non-small-cell lung cancer

Djureinovic, Dijana; Hallström, Björn M; Horie, Masafumi; Mattsson, Johanna Sofia Margareta; La Fleur, Linnea; Fagerberg, Linn; Brunnström, Hans LU ; Lindskog, Cecilia; Madjar, Katrin and Rahnenführer, Jörg, et al. (2016) In JCI insight 1(10). p.86837-86837
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... (More)

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.

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@article{3687da84-9d50-43d9-a33a-43eb33c48795,
  abstract     = {<p>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.</p>},
  author       = {Djureinovic, Dijana and Hallström, Björn M and Horie, Masafumi and Mattsson, Johanna Sofia Margareta and La Fleur, Linnea and Fagerberg, Linn and Brunnström, Hans and Lindskog, Cecilia and Madjar, Katrin and Rahnenführer, Jörg and Ekman, Simon and Ståhle, Elisabeth and Koyi, Hirsh and Brandén, Eva and Edlund, Karolina and Hengstler, Jan G and Lambe, Mats and Saito, Akira and Botling, Johan and Pontén, Fredrik and Uhlén, Mathias and Micke, Patrick},
  issn         = {2379-3708},
  keyword      = {Journal Article},
  language     = {eng},
  month        = {07},
  number       = {10},
  pages        = {86837--86837},
  series       = {JCI insight},
  title        = {Profiling cancer testis antigens in non-small-cell lung cancer},
  url          = {http://dx.doi.org/10.1172/jci.insight.86837},
  volume       = {1},
  year         = {2016},
}