Comprehensive analysis of the role of pyroptosis-related genes in predicting prognosis in hepatocellular carcinoma

Abstract

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Pyroptosis is an inflammatory form of programmed cell death closely related to tumor formation and development. However, the functional role and significance of pyroptosis in HCC remain unclear. Methods RNA-sequencing and clinical data for HCC patients were obtained from TCGA and GEO databases. We first explored the 49 pyroptosis-related genes (PRGs) expression patterns in HCC. The univariate Cox regression analysis and consensus clustering by PRGs were then performed to divide TCGA-HCC patients into two subtypes, C1 and C2. Based on prognostic PRGs, the LASSO Cox regression method was employed to construct a prognostic model. The predictive value was evaluated by generated nomogram and decision curve analysis (DCA). GSEA and immune infiltration analysis evaluated immune status. Additionally, regulating networks of prognostic PRGs were predicted with Networkanalyst online tools. Finally, the expression of the prognostic genes was validated by qRT-PCR. Results HCC patients in subtype C2 exhibited a larger proportion of grade III-IV, higher immune scores, more genetic mutations, and increased expression of immune factors. A prognostic model was developed based on four prognostic PRGs and classified HCC patients into high- and low-risk groups. Patients in the low-risk group showed better prognostic survival. The risk score of this model was an independent prognostic factor and had a good predictive ability. Besides, immune status showed a difference between the two risk groups. We drew the regulating networks between the mRNA of 4 prognostic PRGs and TFs, miRNAs, or chemicals. The qRT-PCR results demonstrated PRGs highly expressed in paracancerous tissues and lowly expressed in carcinoma. Conclusions The prognostic model based on four PRGs has significant implications for prognosis assessment and provides a new idea for HCC treatment.