Comprehensive genomic signature of pyroptosis-related genes and relevant characterization in hepatocellular carcinoma

Sheng Wang; Songsen Gao; Liang Shan; Xueyi Qian; Jiajie Luan; Xiongwen Lv

doi:10.7717/peerj.14691

Comprehensive genomic signature of pyroptosis-related genes and relevant characterization in hepatocellular carcinoma

PeerJ. 2023 Jan 12:11:e14691. doi: 10.7717/peerj.14691. eCollection 2023.

Authors

Sheng Wang^{1

2}, Songsen Gao³, Liang Shan², Xueyi Qian¹, Jiajie Luan¹, Xiongwen Lv²

Affiliations

¹ Department of Pharmacy, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, China.
² The Key Laboratory of Anti-Inflammatory and Immune Medicines, Ministry of Education, Anhui Province Key Laboratory of Major Autoimmune Diseases, School of Pharmacy, Institute for Liver Disease, Anhui Medical University, Hefei, Anhui, China.
³ Department of Orthopedics (Spinal Surgery), The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

Abstract

Background: Currently, the most predominant type of liver cancer is hepatocellular carcinoma (HCC), which is also the fourth leading cause of cancer-related death in the global population. Pyroptosis is an emerging form of cell death that affects the prognosis of cancer patients by modulating tumor cell migration, proliferation and invasion. However, the evaluation of pyroptosis in the prognosis of HCC is still insufficient.

Methods: A total of 365 HCC patients from the TCGA-LIHC cohort were classified into two distinct subtypes using consensus clustering of pyroptosis-related genes (PRGs). Following univariate Cox analysis of differentially expressed genes between subtypes, we established a prognostic model (PRGs-score, PRGS) by LASSO Cox analysis. We further tested the predictive power of the prognostic model in the ICGC (LIRI-JP) and GEO (GSE14520) cohorts. The tumor microenvironment (TME) was studied using the CIBERSORT. The enrichment scores for immune cells and immune functions in low- and high-PRGS groups were assessed using ssGSEA. The IMvigor210 cohort was used to investigate the immunotherapy efficacy. Furthermore, we validated the expression of prognostic genes in PRGS by RT-qPCR in vitro.

Results: The subtyping of HCC based on PRGs exhibited distinct clinical characteristics. We developed a prognostic model PRGS by differentially expressed genes between different subtypes. The results showed that PRGS could well forecast the survival of HCC patients in different cohorts and was associated with the immune microenvironment. Moreover, PRGS was considered to be an independent prognostic risk factor and superior to other pyroptosis-related signatures. Low-PRGS implied greater immune cell infiltration and better overall survival with immunotherapy. The results of RT-qPCR also showed that prognostic genes were significantly dysregulated in HCC.

Conclusions: PRGS has promising application in forecasting the prognosis of HCC patients, and its relationship with the immune microenvironment provides a basis for the subsequent treatment and research of HCC.

Keywords: Hepatocellular carcinoma; Immune microenvironment; Immunotherapy; Prognosis; Pyroptosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Hepatocellular* / genetics
Cell Death
Genomics
Humans
Liver Neoplasms* / genetics
Pyroptosis / genetics
Tumor Microenvironment / genetics

Associated data

figshare/10.6084/m9.figshare.21732488.v1

Grants and funding

This study was funded by the National Natural Science Foundation of China (Grant Nos. 82200662, 81270498 and 81970518), the 2016 Annual Leading Talent Introduction and Cultivation Project in Universities (Grant No. gxbjZD2016032), the Nature and Science Fund from Wannan Medical College, China (Grant No. WK2022F04 and WKS201917), the Science and Technology Research Project of Anhui Province (Grant No. 1604a0802097), and the Natural Science Foundation of Anhui Province (Grant No. 1608085MH178). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.