Research Paper Volume 11, Issue 6 pp 1633—1647

Gene signatures and prognostic values of m6A regulators in clear cell renal cell carcinoma – a retrospective study using TCGA database

Jingcheng Zhou 1, 2, 3, *, , Jiangyi Wang 4, 5, *, , Baoan Hong 1, 2, 3, , Kaifang Ma 1, 2, 3, , Haibiao Xie 1, 2, 3, , Lei Li 1, 2, 3, , Kenan Zhang 1, 2, 3, , Bowen Zhou 1, 2, 3, , Lin Cai 1, 2, 3, , Kan Gong 1, 2, 3, ,

  • 1 Department of Urology, Peking University First Hospital, Beijing, P.R. China
  • 2 Institute of Urology, Peking University, Beijing, P.R. China
  • 3 National Urological Cancer Center, Beijing, P.R. China
  • 4 Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, P.R. China
  • 5 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China
* Equal contribution

received: September 3, 2018 ; accepted: March 6, 2019 ; published: March 15, 2019 ;

https://doi.org/10.18632/aging.101856
How to Cite

Copyright: Zhou et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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 METTL3 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.

Abbreviations

m6A: methylation of N6 adenosine; ccRCC: renal cell carcinoma; TCGA: the Cancer Genome Atlas; CNV: copy number variation; OS: overall survival; DFS: disease-free survival; rRNA: ribosomal RNA: tRNA: transfer RNA: mRNA: messenger RNA; snRNA: small nuclear RNA; GIST: Genomic Identification of Significant Targets in Cancer; AML: acute myelocytic leukemia; ROS: reactive oxygen species; HIF-α: hypoxia induced factor-α; VHL: von Hippel-Lindau; GSEA: gene set enrichment analysis.