Comprehensive characterization of cancer-testis genes in testicular germ cell tumor
Comprehensive characterization of cancer-testis genes in testicular germ cell tumor
复制标题
睾丸生殖细胞肿瘤中癌睾基因的综合表征
DOI：
10.1002/cam4.2223
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发表时间：
2019-07-01
期刊：
影响因子：
4
通讯作者：
Hu, Zhibin
中科院分区：
文献类型：
--
作者：
Chang, Yuting;Wang, Xuewei;Hu, Zhibin
癌-睾丸基因是一组在睾丸和多种癌症中限制性表达的基因，可作为候选驱动基因参与肿瘤的发生发展。我们以前的研究在非生殖细胞肿瘤中发现了一些CT基因，但它们在睾丸生殖细胞肿瘤(TGCT)中的表达模式仍然很不清楚，TGCT是一种基因组变化较少的癌症类型。在这项研究中，我们利用UCSC Xena平台、癌症基因组图谱(TCGA)和基因-组织表达(GTEx)计划的数据集，系统地研究了CT基因在TGCT样本中的表达模式，并评估了TGCT与正常睾丸组织之间的转录组差异。通过途径浓缩分析和生存分析评价表达的CT基因的生物学功能和预后效果。我们鉴定了1036个睾丸特异表达的蛋白编码基因和863个睾丸特异表达的长非编码RNA(LncRNAs)，其中包括883个CT蛋白编码基因和710个先前定义的CT lncRNAs。以KIT、KRAS和NRAS基因突变为特征的精原细胞瘤CT基因表达显著增加(P=3.48×10(-13))。而CT基因的表达与拷贝数改变的基因组比例呈中度负相关(COR=-0.28，P=1.20×10(-3))。与其他癌症不同的是，我们的分析显示，96.16%的CT基因在TGCT样本中下调，而干细胞维持相关途径中的CT基因上调。进一步的生存分析表明，以无病间期和无进展间期为临床终点，CT基因也可以预测TGCT患者的预后。综上所述，我们的研究提供了CT基因在TGCT中的全球视角，并为CT基因在TGCT的进展和维持中发挥重要作用提供了证据。
Cancer-testis (CT) genes are a group of genes restrictedly expressed in testis and multiple cancers and can serve as candidate driver genes participating in the development of cancers. Our previous study identified a number of CT genes in nongerm cell tumors, but their expression pattern in testicular germ cell tumor (TGCT), a cancer type characterized by less genomic alterations, remained largely unknown. In this study, we systematically investigated the expression pattern of CT genes in TGCT samples and evaluated the transcriptome difference between TGCT and normal testis tissues, using datasets from the UCSC Xena platform, The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project. Pathway enrichment analysis and survival analysis were conducted to evaluate the biological function and prognostic effect of expressed CT genes. We identified that 1036 testis-specific expressed protein-coding genes and 863 testis-specific expressed long noncoding RNAs (lncRNAs) were expressed in TGCT samples, including 883 CT protein-coding genes and 710 CT lncRNAs defined previously. The number of expressed CT genes was significantly higher in seminomas (P = 3.48 x 10(-13)) which were characterized by frequent mutations in driver genes (KIT, KRAS and NRAS). In contrast, the number of expressed CT genes showed a moderate negative correlation with the fraction of copy number altered genomes (cor = -0.28, P = 1.20 x 10(-3)). Unlike other cancers, our analysis revealed that 96.16% of the CT genes were down-regulated in TGCT samples, while CT genes in stem cell maintenance related pathways were up-regulated. Further survival analysis provided evidence that CT genes could also predict the prognosis of TGCT patients with both disease-free interval and progression-free interval as clinical endpoints. Taken together, our study provided a global view of CT genes in TGCT and provided evidence that CT genes played important roles in the progression and maintenance of TGCT.