Promoter DNA methylation analysis reveals a novel diagnostic CpG-based biomarker and RAB25 hypermethylation in clear cell renel cell carcinoma

Sci Rep. 2017 Oct 27;7(1):14200. doi: 10.1038/s41598-017-14314-y.

Abstract

Clear-cell renal cell carcinoma (ccRCC) is a common aggressive urinary malignant tumor that cannot be easily diagnosed at an early stage. The DNA methylation occurs within promoter before precancerous lesion plays a pivotal role that could help us in diagnosing and understanding ccRCC. In this study, based on a whole-genome promoter DNA methylation profiling, we used shrunken centroids classifier method to identify a CpG-based biomarker that is capable of differentiating between ccRCC tumor and adjacent tissues. The biomarker was validated in 19 ccRCCs and three public datasets. We found that both CYP4B1 and RAB25 are downregulated with promoter hypermethylation and CA9 is upregulated with promoter hypomethylation, and we validated their mRNA differential expressions in 19 ccRCCs and 10 GEO datasets. We further confirmed that hypermethylated RAB25 is inversely correlated with its mRNA level. Log-rank test showed that ccRCC patients with low levels of CA9 promoter methylation had a higher survival rate. This reveals clinically a potential biomarker for use in early detection for ccRCC, and provides a better understanding of carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / genetics
  • Aryl Hydrocarbon Hydroxylases / genetics
  • Biomarkers, Tumor / genetics*
  • Carbonic Anhydrase IX / genetics
  • Carcinoma, Renal Cell / diagnosis
  • Carcinoma, Renal Cell / genetics*
  • CpG Islands / genetics*
  • DNA Methylation*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kidney Neoplasms / diagnosis
  • Kidney Neoplasms / genetics*
  • Male
  • Middle Aged
  • Promoter Regions, Genetic / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Survival Analysis
  • rab GTP-Binding Proteins / genetics*

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • RNA, Messenger
  • Rab25 protein, human
  • Aryl Hydrocarbon Hydroxylases
  • cytochrome P-450 CYP4B1
  • rab GTP-Binding Proteins
  • CA9 protein, human
  • Carbonic Anhydrase IX