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

INTRODUCTION: 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. METHODS: The present study used various online databases for analysis, and the findings were validated via immunohistochemical (IHC) analysis of HCC patient samples (n=60). RESULTS: 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. CONCLUSION: 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.