Comprehensive genomic signature of pyroptosis-related genes and relevant characterization in hepatocellular carcinoma
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 c...
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PeerJ Inc.
2023-01-01
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| author | Sheng Wang Songsen Gao Liang Shan Xueyi Qian Jiajie Luan Xiongwen Lv |
| author_facet | Sheng Wang Songsen Gao Liang Shan Xueyi Qian Jiajie Luan Xiongwen Lv |
| author_sort | Sheng Wang |
| collection | DOAJ |
| description | 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. |
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| last_indexed | 2024-03-09T07:55:46Z |
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| spelling | doaj.art-8521462baf0c4656966f52933c4bd7bf2023-12-03T01:05:10ZengPeerJ Inc.PeerJ2167-83592023-01-0111e1469110.7717/peerj.14691Comprehensive genomic signature of pyroptosis-related genes and relevant characterization in hepatocellular carcinomaSheng Wang0Songsen Gao1Liang Shan2Xueyi Qian3Jiajie Luan4Xiongwen Lv5Department of Pharmacy, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, ChinaDepartment of Orthopedics (Spinal Surgery), The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaThe 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, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, ChinaThe 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, ChinaBackground 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.https://peerj.com/articles/14691.pdfHepatocellular carcinomaPyroptosisPrognosisImmune microenvironmentImmunotherapy |
| spellingShingle | Sheng Wang Songsen Gao Liang Shan Xueyi Qian Jiajie Luan Xiongwen Lv Comprehensive genomic signature of pyroptosis-related genes and relevant characterization in hepatocellular carcinoma PeerJ Hepatocellular carcinoma Pyroptosis Prognosis Immune microenvironment Immunotherapy |
| title | Comprehensive genomic signature of pyroptosis-related genes and relevant characterization in hepatocellular carcinoma |
| title_full | Comprehensive genomic signature of pyroptosis-related genes and relevant characterization in hepatocellular carcinoma |
| title_fullStr | Comprehensive genomic signature of pyroptosis-related genes and relevant characterization in hepatocellular carcinoma |
| title_full_unstemmed | Comprehensive genomic signature of pyroptosis-related genes and relevant characterization in hepatocellular carcinoma |
| title_short | Comprehensive genomic signature of pyroptosis-related genes and relevant characterization in hepatocellular carcinoma |
| title_sort | comprehensive genomic signature of pyroptosis related genes and relevant characterization in hepatocellular carcinoma |
| topic | Hepatocellular carcinoma Pyroptosis Prognosis Immune microenvironment Immunotherapy |
| url | https://peerj.com/articles/14691.pdf |
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