Fig. 1: DNA methylation patterns associated with hepatocarcinogenesis.

In non-cancerous hepatocytes, the genome-wide methylation and relatively unmethylated CpG island in the promoter of tumor suppressor genes suppress oncogenic expression and enable the expression of tumor suppressive pathways, respectively. In contrast, HCC is characterized by global hypomethylation, which may lead to the activation of oncogenes, e.g., the C/EBPβ gene, contributing to tumor progression as demonstrated by greater histopathological grades and tumor sizes. Additionally, hypermethylation at the promoter regions results in the silencing of tumor suppressor genes, e.g., ZNF334, HIC1, GSTP1, SOCS1, RASSF1, CDKN2A, APC, RUNX3, PRDM2. Hypermethylation at genomic regions known as methylated-in-tumor (MINT) 1, 2, 12, 31 loci are associated with hepatocarcinogenesis. These methylation changes underscore the complex regulatory mechanisms that drive the transition from normal liver function to malignant transformation.