A comprehensive study on the prognostic value of pyroptosis-associated genes in hepatocellular carcinoma

Abstract

Aim: Hepatocellular carcinoma (HCC) is a prevalent malignancy globally, and pyroptosis, an inflammatory form of programmed cell death, is closely associated with tumor progression. The aim of this study is to explore the functional role of pyroptosis in HCC progression.

Methods: RNA sequencing and clinical data of HCC patients from TCGA and GEO databases were analyzed. We examined the expression patterns of 49 pyroptosis-related genes (PRGs) in HCC. Univariate Cox regression and consensus clustering divided TCGA-HCC patients into two subtypes, C1 and C2. A prognostic model was developed using LASSO Cox regression based on significant PRGs, and predictive value was assessed through nomogram and decision curve analysis (DCA). GSEA and immune infiltration analysis were conducted to evaluate immune status. Additionally, Networkanalyst tools were used to predict regulating networks of PRGs, and gene expression was validated using qRT-PCR.

Results: Subtype C2 showed higher grades (III-IV), immune scores, genetic mutations, and increased immune factor expression. A prognostic model based on four prognostically relevant PRGs stratified HCC patients into high- and low-risk groups. The low-risk group had better survival. The risk score was an independent prognostic factor with strong predictive ability. Immune status differed between the two risk groups. Regulatory networks between PRGs, transcription factors (TFs), miRNAs, and chemicals were identified. qRT-PCR confirmed higher expression of PRGs in paracancerous tissues compared to carcinoma.

Conclusion: A prognostic model based on four PRGs offers significant implications for prognosis assessment and could inform HCC treatment strategies.

Keywords

Hepatocellular carcinoma / pyroptosis / prognosis / immunity

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