Pyroptosis was recently demonstrated to be an inflammatory form of gasdermin-regulated programmed cell death characterized by cellular lysis and the release of several proinflammatory factors and participates in
tumorigenesis. However, the effects of pyroptosis-related long noncoding RNAs (lncRNAs) on
hepatocellular carcinoma (HCC) have not yet been completely elucidated. Based on the regression coefficients of ZFPM2-AS1, KDM4A-AS1, LUCAT1, NRAV, CRYZL2P-SEC16B, AL031985.3, SNHG4, AL049840.5, AC008549.1, MKLN1-AS, AC099850.3, and LINC01224, HCC patients were classified into a low- or high-risk group. The high-risk score according to pyroptosis-related
lncRNA signature was significantly associated with poor overall survival even after adjusting for age and clinical stage. Receiver operating characteristic curves and principal component analysis further supported the accuracy of the model. Our study revealed that a higher pyroptosis-related
lncRNA risk score was significantly associated with
tumor staging, pathological grade, and
tumor-node-
metastasis stages. The nomogram incorporating the pyroptosis-related
lncRNA risk score and clinicopathological factors demonstrated good accuracy. Furthermore, we observed distinct tumor microenvironment cell infiltration characteristics between high- and low-risk
tumors. Notably, based on the risk model, we found that the risk score is closely related to the expression of immune checkpoint genes, immune subtypes of
tumors, and the sensitivity of HCC to
chemotherapy drugs and
immunotherapy. In conclusion, our novel risk score of pyroptosis-related
lncRNA can serve as a promising prognostic
biomarker for HCC patients and provide help for HCC patients to guide precision drug treatment and
immunotherapy.