Identifying pyroptosis-related lncRNAs to predict prognosis and immune regulation in hepatocellular carcinoma.

BACKGROUND: Immunotherapy is often effective for treating hepatocellular carcinoma (HCC) and is widely used clinically, with variable effectiveness among individuals. PURPOSE: In this study, we aimed to develop a predictive signature from eight pyroptosis-related long non-coding RNAs (PRlncRNAs) for survival forecasting in HCC patients and immunotherapy evaluations. METHODS: To assess the prognostic performance of the risk signature, we performed the following analyses: Kaplan-Meier survival analysis, receiver operator characteristics analysis, and nomogram construction. RESULTS: The results showed that individuals within the high-risk cohort exhibited unfavorable prognosis, with the risk score acting as an independent predictor of prognosis. The PRlncRNAs in the high-risk cohort were significantly gathered in the immune-related signaling pathways; gene set enrichment analysis (GSEA) and single-sample GSEA showed that their functional activities were reliant on the immune cells, inhibitory immune checkpoints, and cytokines. Furthermore, we confirmed that downregulation of LINC00942 (a risk factor) expression increased pyroptosis levels and promoted infiltration of CD3 in HCC, while si-AC009283.1 group (a protective factor) exerted opposite effects in vitro. CONCLUSION: This risk signature developed using eight PRlncRNAs exhibits high reliability for predicting the prognosis of HCC patients and assessing their immune status, emphasizing their crucial roles in guiding immunotherapy and crafting precise treatments for the benefit of patients.