Signature Construction and Molecular Subtype Identification Based on Pyroptosis-Related Genes for Better Prediction of Prognosis in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, there is a lack of adequate means of treatment prognostication for HCC. Pyroptosis is a newly discovered way of programmed cell death. However, the prognostic role of pyroptosis in HCC has not been thoroughly investigated. Here, we generated a novel prognostic signature to evaluate the prognostic value of pyroptosis-related genes (PRGs) using the data from The Cancer Genome Atlas (TCGA) database. The accuracy of the signature was validated using survival analysis through the International Cancer Genome Consortium cohort (n=231) and the First Affiliated Hospital of Wenzhou Medical University cohort (n=180). Compared with other clinical factors, the risk score of the signature was found to be associated with better patient outcomes. The enrichment analysis identified multiple pathways related with pyroptosis in HCC. Furthermore, drug sensitivity testing identified six potential chemotherapeutic agents to provide possible treatment avenues. Interestingly, patients with low risk were confirmed to be associated with lower tumor mutation burden (TMB). However, patients at high risk were found to have a higher count of immune cells. Consensus clustering was performed to identify two main molecular subtypes (named clusters A and B) based on the signature. It was found that compared with cluster B, better survival outcomes and lower TMB were observed in cluster A. In conclusion, signature construction and molecular subtype identification of PRGs could be used to predict the prognosis of HCC, which may provide a specific reference for the development of novel biomarkers for HCC treatment.