Identification of methylation-driven genes related to prognosis in clear-cell renal cell carcinoma

J Cell Physiol. 2020 Feb;235(2):1296-1308. doi: 10.1002/jcp.29046. Epub 2019 Jul 5.

Abstract

With the participation of the existing treatment methods, the prognosis of advanced clear-cell renal cell carcinoma (ccRCC) is poor. More evidence indicates the presence of methylation in ccRCC cancer cells, but there is a lack of studies on methylation-driven genes in ccRCC. We analyzed the open data of ccRCC in The Cancer Genome Atlas database to obtain ccRCC-related methylation-driven genes, and then carried out pathway enrichment, survival, and joint survival analyses. More important, we deeply explored the correlation between differential methylation sites and the expression of these driving genes. Finally, we screened 29 methylation-driven genes via MethylMix, of which six were significantly associated with the survival of ccRCC patients. This study demonstrated that the effect of hypermethylation or hypomethylation on prognosis is different, and the level of methylation of key methylation sites is associated with gene expression. We identified methylation-driven genes independently predicting prognosis in ccRCC, which offers theoretical support in bioinformatics for the study of methylation in ccRCC and a new perspective for the epigenetic study of ccRCC.

Keywords: MethylMix; clear-cell renal cell carcinoma; methylation-driven genes; prognosis; the Cancer Genome Atlas (RRID:SCR_014514).

MeSH terms

  • Biomarkers, Tumor / genetics
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Computational Biology / methods
  • DNA Methylation / physiology
  • Epigenomics
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • Prognosis
  • Promoter Regions, Genetic / genetics*

Substances

  • Biomarkers, Tumor