Pan-cancer analysis of m5C regulator genes reveals consistent epigenetic landscape changes in multiple cancers

Abstract Background 5-Methylcytosine (m5C) is a reversible modification to both DNA and various cellular RNAs. However, its roles in developing human cancers are poorly understood, including the effects of mutant m5C regulators and the outcomes of modified nucleobases in RNAs. Methods Based on The Cancer Genome Atlas (TCGA) database, we uncovered that mutations and copy number variations (CNVs) of m5C regulatory genes were significantly correlated across many cancer types. We then assessed the correlation between the expression of individual m5C regulators and the activity of related hallmark pathways of cancers. Results After validating m5C regulators’ expression based on their contributions to cancer development and progression, we observed their upregulation within tumor-specific processes. Notably, our research connected aberrant alterations to m5C regulatory genes with poor clinical outcomes among various tumors that may drive cancer pathogenesis and/or survival. Conclusion Our results offered strong evidence and clinical implications for the involvement of m5C regulators