A Pyroptosis-Based Prognostic Model for Immune Microenvironment Estimation of Hepatocellular Carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC), an aggressive malignant tumor, has a high incidence and unfavorable prognosis. Recently, the synergistic effect of pyroptosis in antitumor therapy and regulation of tumor immune microenvironment has made it possible to become a novel therapeutic method, but its potential mechanism still needs further exploration. METHODS: Differentially expressed genes with prognostic value in Liver Hepatocellular Carcinoma Project of The Cancer Genome Atlas (TCGA-LIHC) cohort were screened and incorporated into the risk signature by Cox proportional hazards regression model and least absolute shrinkage and selection operator. Kaplan-Meier (KM) curves and receiver operating characteristic (ROC) curves were applied to conduct survival comparisons and estimate prediction ability. The dataset of Liver Cancer-RIKEN, Japan Project from International Cancer Genome Consortium (ICGC-LIRI-JP) cohort was used to verify the reliability of the signature. Correlation analysis between clinicopathological characteristics, immune infiltration, drug sensitivities, and risk scores was conducted. Functional annotation analyses were performed for the genes differentially expressed between high-risk and low-risk groups. RESULTS: A risk signature consisting of 6 pyroptosis-related genes in HCC was developed and validated. KM curves and ROC curves revealed its considerable predictive accuracy. Higher risk scores meant more advanced grade, higher alpha-fetoprotein level, and stronger invasive ability. Overexpressed genes in high-risk population were more enriched in the immune-associated pathways, and these patients might be more sensitive to immune checkpoint inhibitors instead of Sorafenib. Intriguingly, 6 identified genes were promising to be prognostic biomarkers and therapeutic targets of HCC. CONCLUSIONS: The signature may have crucial clinical significance in predicting survival prognosis, immune infiltration, and drug efficacy based on pyroptosis-related genes.