A Global Gene Body Methylation Measure Correlates Independently with Overall Survival in Solid Cancer Types

Abstract

Epigenetics, CpG methylation of CpG islands (CGI) and gene bodies (GBs), plays an important role in gene regulation and cancer biology, the former established as a transcription regulator. Genome wide CpG methylation, summarized over GBs and CGIs, was analyzed for impact on overall survival (OS) in cancer. The averaged GB and CGI methylation status of each gene was categorized into methylated and unmethylated (defined) or undefined. Differentially methylated GBs and genes associated with their GB methylation status were compared to the corresponding CGI methylation states and biologically annotated. No relevant correlations of GB and CGI methylation or GB methylation and gene expression were observed. Summarized GB methylation showed impact on OS in ovarian, breast, colorectal, and pancreatic cancer, and glioblastoma, but not in lung cancer. In ovarian, breast, and colorectal cancer more defined GBs correlated with unfavorable OS, in pancreatic cancer with favorable OS and in glioblastoma more methylated GBs correlated with unfavorable OS. The GB methylation of genes were similar over different samples and even over cancer types; nevertheless, the clustering of different cancers was possible. Gene expression differences associated with summarized GB methylation were cancer specific. A genome-wide dysregulation of gene-body methylation showed impact on the outcome in different cancers.