Zhou Jingcheng, Wang Jiangyi, Hong Baoan, Ma Kaifang, Xie Haibiao, Li Lei, Zhang Kenan, Zhou Bowen, Cai Lin, Gong Kan
Department of Urology, Peking University First Hospital, Beijing, P.R. China.
Institute of Urology, Peking University, Beijing, P.R. China.
Aging (Albany NY). 2019 Mar 15;11(6):1633-1647. doi: 10.18632/aging.101856.
m6A is the most common form of mRNA modification. However, little is known about its role in clear cell renal cell carcinoma (ccRCC). This study aims to identify gene signatures and prognostic values of m6A regulators in ccRCC. In this study, a total of 528 ccRCC patients from TCGA database with sequencing and CNV data were included. Survival analysis was performed using log-rank tests and Cox regression model. The association between alteration of m6A regulators and clinicopathological characteristics was examined using chi-square test. The results showed that alteration of m6A regulators was associated with pathologic stage. Patients with any CNVs of the regulatory genes had worse OS and DFS than those with diploid genes. Moreover, deletion of m6A "writer" genes was an independent risk factor for OS, and copy number gain of "eraser" genes could magnify the effect in a synergistic way. Additionally, low expression of the writer gene was related to activations of adipogenesis and mTOR pathways. Thus, we for the first time determined genetic alterations of m6A regulators in ccRCC and found a significant relationship between the alterations and worse clinical characteristics. The findings provide us clues to understand epigenetic modification of RNA in ccRCC.
m6A是mRNA修饰最常见的形式。然而,其在肾透明细胞癌(ccRCC)中的作用却鲜为人知。本研究旨在确定ccRCC中m6A调节因子的基因特征和预后价值。本研究纳入了来自TCGA数据库的528例有测序和CNV数据的ccRCC患者。使用对数秩检验和Cox回归模型进行生存分析。采用卡方检验研究m6A调节因子改变与临床病理特征之间的关联。结果显示,m6A调节因子的改变与病理分期相关。调节基因存在任何CNV的患者的总生存期(OS)和无病生存期(DFS)均比二倍体基因患者差。此外,m6A“书写器”基因的缺失是OS的独立危险因素,“擦除器”基因的拷贝数增加可协同放大这种效应。此外,书写器基因的低表达与脂肪生成和mTOR通路的激活有关。因此,我们首次确定了ccRCC中m6A调节因子的基因改变,并发现这些改变与较差的临床特征之间存在显著关系。这些发现为我们理解ccRCC中RNA的表观遗传修饰提供了线索。