RACGAP1 and MKI67 are potential prognostic biomarker in hepatocellular carcinoma caused by HBV/HCV via lactylation

Hepatocellular carcinoma (HCC) is recognized as the prime and lethal form of liver cancer caused by the hepatitis B virus (HBV) and hepatitis C virus (HCV) globally. Lactate is an end product of glycolysis that influences epigenetic expression through histone lactylation. While MKI67 and RACGAP1 play crucial roles in HBV- and HCV-related HCC. However, the role of lactylation-related genes (LRGs) effects in this context remains unclear. This study innovatively explored the role of LRGs in HBV/HCV-associated HCC, identifying novel biomarkers for diagnosis and prognosis. The present study used various online databases for analysis, and the findings were validated via immunohistochemical (IHC) analysis of HCC patient samples (n=60). We identified six signature LRGs (ALB, G6PD, HMGA1, MKI67, RACGAP1, and RFC4) possess prognostic potential, correlation with immune infiltration, and lactylation-related pathways, providing novel insights into tumor microenvironment (TME) of HCC. Moreover, MKI67 and RACGAP1 were significantly associated with HBV- and HCV-related HCC. IHC confirmed these findings, with high expression of MKI67 and RACGAP1 was significantly linked with HBV/HCV-associated HCC compared to non-viral HCC. The expression is also significantly associated with key clinical variables. Our results suggest that MKI67 and RACGAP1 could serve as promising biomarkers for detecting and predicting HCC caused by HBV/HCV via lactylation, opening a new direction for immune-targeted therapies.