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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 orcid ; Lindskog, Cecilia ; Madjar, Katrin and Rahnenführer, Jörg , et al. (2016) In JCI Insight 1(10).
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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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Journal Article
in
JCI Insight
volume
1
issue
10
article number
e86837
publisher
The American Society for Clinical Investigation
external identifiers
  • pmid:27699219
  • scopus:85071293611
ISSN
2379-3708
DOI
10.1172/jci.insight.86837
language
English
LU publication?
no
id
3687da84-9d50-43d9-a33a-43eb33c48795
alternative location
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5033889/
date added to LUP
2017-07-13 09:51:30
date last changed
2024-06-09 18:36:46
@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}},
  keywords     = {{Journal Article}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{10}},
  publisher    = {{The American Society for Clinical Investigation}},
  series       = {{JCI Insight}},
  title        = {{Profiling cancer testis antigens in non-small-cell lung cancer}},
  url          = {{http://dx.doi.org/10.1172/jci.insight.86837}},
  doi          = {{10.1172/jci.insight.86837}},
  volume       = {{1}},
  year         = {{2016}},
}