Unveiling disulfidptosis-related genes in HBV-associated hepatocellular carcinoma: an integrated study incorporating transcriptome and Mendelian randomization analyses.

ABSTRACT

Disulfidptosis, a recently unveiled mechanism of demise, has been linked to an unfavorable prognosis in the context of hepatocellular carcinoma (HCC). However, few studies have focused on the causal link between disulfidptosis and HBV-related HCC (HBV-HCC). In this study, the Mendelian randomization (MR) analysis demonstrated that the risk of HCC increased with increasing genetic susceptibility to HBV, and the genetic changes of disulfidptosis were significantly associated with the increased risk of HBV-HCC. Within both the TCGA and GEO cohorts, it is possible to accurately forecast the prognosis of HBV-HCC by utilizing a risk score that is derived from a combination of GYS1, RPN1, SLC7A11, LRPPRC and CAPZB genes. GYS1, a potential therapeutic target for HBV-HCC, exhibits a remarkable positive correlation with immune infiltration and MSI when compared to other molecules. Furthermore, we demonstrated that silencing GYS1 effectively inhibits the tumor proliferation and metastasis of HBV-HCC in vitro and in vivo. Overall, this study expands the understanding of the potential roles of disulfidptosis in HBV-HCC and highlights GYS1 as a promising target for HBV-HCC.