Identification of a Pyroptosis-Related Gene Signature for Predicting Overall Survival and Response to Immunotherapy in Hepatocellular Carcinoma

Susu Zheng; Xiaoying Xie; Xinkun Guo; Yanfang Wu; Guobin Chen; Xiaochun Chen; Meixia Wang; Tongchun Xue; Boheng Zhang

doi:10.3389/fgene.2021.789296

Identification of a Pyroptosis-Related Gene Signature for Predicting Overall Survival and Response to Immunotherapy in Hepatocellular Carcinoma

Front Genet. 2021 Dec 3:12:789296. doi: 10.3389/fgene.2021.789296. eCollection 2021.

Authors

Susu Zheng^{1

2}, Xiaoying Xie^{1

2}, Xinkun Guo¹, Yanfang Wu¹, Guobin Chen¹, Xiaochun Chen¹, Meixia Wang¹, Tongchun Xue², Boheng Zhang^{1

2

3}

Affiliations

¹ Department of Hepatic Oncology, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, China.
² Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, Zhongshan Hospital and Shanghai Medical School, The Liver Cancer Institute, Fudan University, Shanghai, China.
³ Center for Evidence-based Medicine, Shanghai Medical School, Fudan University, Shanghai, China.

Abstract

Pyroptosis is a novel kind of cellular necrosis and shown to be involved in cancer progression. However, the diverse expression, prognosis and associations with immune status of pyroptosis-related genes in Hepatocellular carcinoma (HCC) have yet to be analyzed. Herein, the expression profiles and corresponding clinical characteristics of HCC samples were collected from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Then a pyroptosis-related gene signature was built by applying the least absolute shrinkage and selection operator (LASSO) Cox regression model from the TCGA cohort, while the GEO datasets were applied for verification. Twenty-four pyroptosis-related genes were found to be differentially expressed between HCC and normal samples. A five pyroptosis-related gene signature (GSDME, CASP8, SCAF11, NOD2, CASP6) was constructed according to LASSO Cox regression model. Patients in the low-risk group had better survival rates than those in the high-risk group. The risk score was proved to be an independent prognostic factor for overall survival (OS). The risk score correlated with immune infiltrations and immunotherapy responses. GSEA indicated that endocytosis, ubiquitin mediated proteolysis and regulation of autophagy were enriched in the high-risk group, while drug metabolism cytochrome P450 and tryptophan metabolism were enriched in the low-risk group. In conclusion, our pyroptosis-related gene signature can be used for survival prediction and may also predict the response of immunotherapy.

Keywords: hepatocellular carcinoma; immune checkpoint inhibitors; immune infiltrates; prognosis; pyroptosis.