Profiling cancer testis antigens in non-small-cell lung cancer
Profiling cancer testis antigens in non-small-cell lung cancer
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DOI：
10.1172/jci.insight.86837
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发表时间：
2016-07-07
期刊：
影响因子：
8
通讯作者：
Micke, Patrick
中科院分区：
文献类型：
--
作者：
Djureinovic, Dijana;Hallstrom, Bjorn M.;Micke, Patrick
睾丸癌抗原（cta）作为生物标志物具有重要的临床价值，是免疫治疗的重要靶点。为了全面表征非小细胞肺癌（NSCLC）的CTA特征，我们将199个NSCLC组织的RNAseq数据与来自32个不同正常器官的142个样本的正常转录组进行了比较。目前在癌症睾丸数据库（CTdatabase）中注释的232例cta中，有96例在NSCLC中得到证实。为了获得非小细胞肺癌的无偏CTA图谱，我们对RNAseq数据集应用了严格的标准，并将90个基因定义为CTA，其中55个基因未在ct数据库中注释，因此代表了潜在的新CTA。聚类分析显示，CTA表达具有组织学依赖性，并发表达较为常见。IHC证实了选定的新cta （TKTL1, TGIF2LX， VCX和CXORF67）的组织特异性蛋白表达。此外，基于癌症基因组图谱的独立数据，甲基化被确定为CTA表达的调控机制。无论是在我们的RNAseq队列中，还是在1117例非小细胞肺癌病例的独立荟萃分析中，cta对肺癌预后的影响都没有得到证实。总之，我们定义了一组90个可靠的cta，包括蛋白质表达、甲基化和生存关联的信息。详细的RNAseq目录可以指导生物标志物的研究和努力确定免疫治疗策略的目标。
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.