Role of mC-related regulatory genes in the diagnosis and prognosis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignancies globally, and is frequently associated with a poor prognosis. 5-methylcytosine (mC) is a common epigenetic modification with many critical roles in eukaryotes. However, the expression and functional roles of mC regulators are largely unknown. In this study, we utilized The Cancer Genome Atlas (TCGA) to determine the expression, gene signatures, and prognostic values of mC-related genes. We confirmed that the frequency of mutation events of mC regulatory genes was high in HCC (35/363). Dysregulation of mC-related genes was also associated with a higher HCC stage. Moreover, a strong relationship was found between the expression of mC regulatory genes and HCC patient survival. High expression of and correlated significantly with survival outcome. We developed a two-gene signature of mC regulators with HCC prognostic value based on the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression models. Gene set enrichment analysis (GSEA) results indicated that high expression of was associated with methylation and demethylation processes. Meanwhile, high expression of was clearly related to cell cycle regulation and mitosis. In conclusion, our results revealed that mC-related genes play an essential role in tumor progression in HCC. Further detection of mC methylation could provide a novel method for HCC targeted therapy.