Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan; #2 Yude Road, Taichung 40447, Taiwan.
Division of General Pediatrics, China Medical University Children's Hospital, Taichung 40447, Taiwan.
Int J Mol Sci. 2018 May 28;19(6):1586. doi: 10.3390/ijms19061586.
The nucleotide degrading enzyme gene (ribonuclease H2 subunit A) has been found to be overexpressed in cancers. Our aim was to understand the role of in cancer prognostication and to establish a scoring system based on the expressions of genes interacting with We screened the nucleotide degrading enzyme gene expression in RNAseq data of 14 cancer types derived from The Cancer Genome Atlas (TCGA) and found that overexpression was associated with poor patient survival only in renal cell carcinomas (RCCs). Further cluster analyses of samples with poor outcomes revealed that cluster of differentiation 151 () upregulation correlated with low cyclin dependent kinase 1 () and high expression. The combination of low expression and high expression resulted in impaired proliferation in four kidney cancer cell lines, suggesting potential synthetic dosage lethality (SDL) interactions between the two genes. A prognostication scoring system was established based on the expression levels of , , and related genes, which could effectively predict the overall survival in a TCGA clear cell RCC cohort ( = 533, 995.3 versus 2242.2 days, < 0.0001), in another clear cell renal cell carcinoma (ccRCC) cohort E-GEOD-22541 ( = 44, 390.0 versus 1889.2 days, = 0.0007), and in a TCGA papillary RCC (pRCC) cohort ( = 287, 741.6 versus 1623.7 days, < 0.0001). Our results provide a clinically applicable prognostication scoring system for renal cancers.
核苷酸降解酶基因（核糖核酸酶 H2 亚基 A）已被发现在癌症中过度表达。我们的目的是了解在癌症预后中的作用，并建立一个基于与相互作用的基因表达的评分系统。我们筛选了来自癌症基因组图谱（TCGA）的 14 种癌症类型的 RNAseq 数据中的核苷酸降解酶基因表达，发现仅在肾细胞癌（RCC）中，过表达与患者生存不良相关。对预后不良样本的进一步聚类分析显示，分化簇 151（）上调与细胞周期蛋白依赖性激酶 1（）低和高表达相关。四种肾癌细胞系中低表达和高表达的组合导致增殖受损，表明这两个基因之间可能存在合成剂量致死性（SDL）相互作用。基于表达水平建立了预后评分系统，可有效预测 TCGA 透明细胞 RCC 队列（=533，995.3 与 2242.2 天，<0.0001）、另一个透明细胞肾细胞癌（ccRCC）队列 E-GEOD-22541（=44，390.0 与 1889.2 天，=0.0007）和 TCGA 乳头状 RCC（pRCC）队列（=287，741.6 与 1623.7 天，<0.0001）的总生存率。我们的研究结果为肾癌提供了一种临床应用的预后评分系统。
