Predicting the prognosis of hepatocellular carcinoma based on the interaction between pyroptosis, apoptosis, and necroptosis.

Abstract

Multiple programmed cell death pathways (pyroptosis, apoptosis, and necroptosis) are closely related to the progression of hepatocellular carcinoma (HCC). Furthermore, molecular interactions among pyroptotic, apoptotic, and necroptotic components may be new targets for cancer therapy. However, the signature of the genes involved in the interaction between pyroptosis, apoptosis, and necroptosis (PANRGs), and their prognostic value, is still unclear in HCC. In this study, we used HCC clinical and expression data from TCGA and GEO to explore the relationship between PANRGs and HCC. First, we determined the copy number variation incidence of 41 PANRGs genes and explored the prognostic correlation of these genes in HCC. Based on PANRGs, two molecular subgroups of HCC associated with prognosis were identified. We also found significant differences in the overall survival time and the immune infiltration of HCC patients between the two subgroups. Finally, based on the nine PANRGs (CDC25B, EZH2, HMOX1, PLK1, SQSTM1, WEE1, TREM2, MYCN, and FLT3), we constructed a prognostic model using LASSO-Cox regression analysis. The prognostic model could predict OS of HCC patients in TCGA and GEO cohorts with high accuracy. Significant correlations were found between prognosis-related PANRGs and the tumor immune microenvironment (TIME), tumor mutational burden (TMB), and drug sensitivity. In conclusion, we explored the role of PANRGs in HCC and the association of these genes with TIME, TMB, and drug sensitivity.