Life span-associated ferroptosis-related genes identification and validation for hepatocellular carcinoma patients as hepatitis B virus carriers.

BACKGROUND: Hepatitis B virus (HBV)-infected population accounts for approximately 50% of all hepatocellular carcinoma (HCC) cases and has a relatively poor prognosis. Although the significant role of ferroptosis in the development and therapeutic response of various cancers has been validated, the key ferroptosis-related genes (FRGs) on the stratification of HBV-associated HCC are still unclear.

METHODS: Through the random forest, GSVA and Cox regression analyses, we established a comprehensive prognostic system covering multiple FRGs to elevate the predictive accuracy for the survival rate of HBV-related HCC using information obtained from public databases. The association between key FRGs and the immune microenvironment was evaluated, and the molecular mechanism was identified by GSEA and SNV analyses. Finally, the differential expression of key FRGs was validated by immunohistochemistry staining of patient tissue microarrays.

RESULTS: Within the top 10 key FRGs, EPAS1 and GABARAPL1 were taken as protective factors, and SQLE, RAD51AP1, RPL8, CAPG, RRM2, SLC1A5, SLC38A1, and SRC were the other eight dangerous markers. Cox regression analysis combined with clinicopathological features indicated the independent prognostic efficacy of GSVA complex score based on these FRGs. In addition, key FRGs were related to immune and metabolic-related functions. Especially, the immunohistochemical analysis of SQLE in 50 clinical samples showed significantly higher expression in HBV+ HCC tissues.

CONCLUSIONS: These results indicate that 10 FRGs may be potential biomarkers and therapeutic targets for long-term survival in HBV-related HCC.