• Low frequency of differentially methylated genes among differentially expressed genes and their positive or negative correlations in colon adenocarcinoma
  • Zohreh Jahanafrooz,1,*
    1. Department of Biology, Faculty of Sciences, University of Maragheh, Maragheh, Iran


  • Introduction: DNA methylation is a regulatory mechanism of gene expression. Disruption in gene expression and DNA methylation are promising cancer biomarkers and therapeutic targets for cancer therapy. The aim of this study was to determine the consistent or conflicting patterns between gene expression and DNA methylation in colon adenocarcinoma (COAD).
  • Methods: Differentially expressed genes (DEGs) (|log2FC| ≥ 1 and p-value < 0.001) and differentially methylated genes (|Δβ| ≥ 0.02 and p-value < 0.001) in COAD were retrieved from the public OncoDB database. Enrichr database was used for the functional evaluation of DEGs.
  • Results: We identified 1414 downregulated and 1402 upregulated genes in COAD. The chemokine signaling pathway and cell cycle were the most significantly enriched pathways of downregulated and overexpressed genes, respectively. 1136 genes showed differential methylation in tumor compared to normal tissues; only 107 of them were among the DEGs. In 55 genes, hyper-methylation was accompanied by a decrease in expression; and 15 overexpressed genes showed hypo-methylated promoter. However, 14 genes showed decreased expression when their promoter hypo-methylated; additionally, 10 upregulated genes showed hyper-methylated promoter.
  • Conclusion: In conclusion, alteration of DNA methylation did not contribute to COAD development exclusively via a direct effect on gene expression. In addition, not all DEGs undergo a change in DNA methylation level, and correlations between methylation level and gene expression could be positive or negative. Other factors such as the location of DNA methylation, non-coding variants, and context of the tumor microenvironment can be involved in gene expression regulation.
  • Keywords: Differentially expressed genes, DNA methylation, Colon adenocarcinoma, OncoDB database