Epigenetic and microRNA Signatures as Predictive Biomarkers in HCV Genotype 4-Induced Liver Cirrhosis and HCC

Abstract Introduction: Hepatocellular carcinoma (HCC) and chronic liver disease (CLD) are mostly linked to hepatitis C virus (HCV) infection, especially genotype 4. The advancement of liver cancer is significantly influenced by epigenetic mechanisms, such as DNA methylation and microRNA regulation. Aim of the study: This study aimed to assess the expression of two tumor suppressor genes in patients infected with HCV genotype 4: glutathione S-transferase pi 1 (GSTP1) and E-cadherin 1 (CDH1). It also aimed to explore the regulatory relationship between these genes and microRNA152 (miRNA152) and DNA methyltransferase 1 (DNMT1) to evaluate their potential roles as biomarkers for HCC development. Methods: Quantitative real-time PCR was done to evaluate the gene expression levels of GSTP1, CDH1, miRNA152, and DNMT1 in CLD and HCC patients infected with HCV genotype 4. Correlation analyses were used to examine regulatory linkage. Results: The results indicated a substantial inverse correlation between DNMT1 and miRNA152. Furthermore, DNMT1 expression exhibited a negative association with both GSTP1 and CDH1, while GSTP1 and CDH1 had a positive correlation. The results indicate that DNMT1 and miRNA152 govern the epigenetic inactivation of tumor suppressor genes. Conclusion: In individuals with HCV genotype 4, the interplay of miRNA152, DNMT1, GSTP1, and CDH1 may contribute to the pathogenesis of HCC. These indicators demonstrate potential roles as therapeutic targets and noninvasive prognostic biomarkers for HCV-related liver disease.