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Life sciences · Journal article
Discover Oncology · September 26, 2026
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Hepatocellular carcinoma (HCC) is a highly malignant solid tumor characterized by a very poor prognosis. Pyroptosis is a new type of programmed cell death that has been associated with cancer in recent studies. However, the expression of pyroptosis-related genes in HCC and their relationship with prognosis are not clear. Expression and clinical data were collected from The Cancer Genome Atlas (TCGA), GSE54236 and local hospitals. Univariate Cox regression analysis and the LASSO Cox regression model established a novel pyroptosis signature based on TCGA. The predictive accuracy of the risk model was assessed by receiver operating characteristic (ROC) analysis, the Kaplan–Meier method, and principal component analysis (PCA). Functional enrichment was performed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and single-sample gene set enrichment analysis ssGSEA. Forty-two pyroptosis-related differentially expressed genes (DEGs) were identified by comparing their expression in HCC and normal tissues, and HCC patients were divided into two clusters by DEGs. A novel pyroptosis-related signature (including CHMP4A, GSDME, CHMP3, CHMP4B, BAK1, NLRP3, and GZMA) was identified, which has good predictive value for HCC prognosis in both TCGA and GEO data sets and is an independent prognostic factor in HCC. The functional enrichment analysis indicated that the pyroptosis-related genes were abundant and immune activity decreased in high-risk groups. The risk model of pyroptosis-related genes is effective and robust in predicting the prognosis of HCC. The model might be related to the dysregulated immune microenvironment and provide new direction for HCC therapy.