Comprehensive analysis of immunogenic cell death associated genes expression, tumor microenvironment, and prognosis in hepatocellular carcinoma
Background: Immunogenic cell death (ICD) plays an important role in the development of cancers. This study attempted to explore the role of ICD in the prognosis of hepatocellular carcinoma (HCC).Methods: Gene expression and clinical data were downloaded from The Cancer Genome Alas and Gene Expressio...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-03-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1122011/full |
| _version_ | 1797871453162438656 |
|---|---|
| author | Jiankang Xiang Chuan Liu Qingmin He Pengzhan He Weiguo Dong |
| author_facet | Jiankang Xiang Chuan Liu Qingmin He Pengzhan He Weiguo Dong |
| author_sort | Jiankang Xiang |
| collection | DOAJ |
| description | Background: Immunogenic cell death (ICD) plays an important role in the development of cancers. This study attempted to explore the role of ICD in the prognosis of hepatocellular carcinoma (HCC).Methods: Gene expression and clinical data were downloaded from The Cancer Genome Alas and Gene Expression Omnibus dataset. The immune/stromal/Estimate scores of the tumor microenvironment (TME) were calculated by ESTIMATE and CIBERSORT algorithms. Kaplan-Meier analysis, functional enrichment analysis, least absolute shrinkage and selection operator (LASSO) analysis, and univariate and multivariate Cox regression analysis were used for prognostic gene screening and prognostic model construction. The correlation of immune cell infiltration and risk scores was analyzed as well. Molecular docking was used to explore the relevance of related genes to anti-cancer drugs.Results: Ten ICD associated differentially expressed genes in HCC were found, and all of them had good predictive ability for HCC. ICD gene high amount of expression group was associated with poor prognosis (p = 0.015). The TME, immune cell infiltration and gene expression were different between ICD high and low groups (all p < 0.05). Six ICD associated genes (BAX, CASP8, IFNB1, LY96, NT5E and PIK3CA) which could predict the survival status were identified and used to construct the prognostic model for HCC. A risk score was calculated and it could be used as an independent prognostic factor in HCC patients (p < 0.001). In addition, the risk score had a positive correlation with macrophage M0 (r = 0.33, p = 0.0086). Molecular docking indicated that sorafenib could bind strongly to the target protein, representing that sorafenib may exert anticancer effects through these six ICD associated genes.Conclusion: This study established a prognostic model including six ICD associated genes for HCC, which may deepen our understanding of ICD and guide therapy for HCC patients. |
| first_indexed | 2024-04-10T00:44:21Z |
| format | Article |
| id | doaj.art-c7634333ebe34f62ae79940f8a265166 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-10T00:44:21Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-c7634333ebe34f62ae79940f8a2651662023-03-14T04:44:56ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-03-011410.3389/fphar.2023.11220111122011Comprehensive analysis of immunogenic cell death associated genes expression, tumor microenvironment, and prognosis in hepatocellular carcinomaJiankang Xiang0Chuan Liu1Qingmin He2Pengzhan He3Weiguo Dong4Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, ChinaHenan Key Laboratory of Helicobacter Pylori and Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, ChinaBackground: Immunogenic cell death (ICD) plays an important role in the development of cancers. This study attempted to explore the role of ICD in the prognosis of hepatocellular carcinoma (HCC).Methods: Gene expression and clinical data were downloaded from The Cancer Genome Alas and Gene Expression Omnibus dataset. The immune/stromal/Estimate scores of the tumor microenvironment (TME) were calculated by ESTIMATE and CIBERSORT algorithms. Kaplan-Meier analysis, functional enrichment analysis, least absolute shrinkage and selection operator (LASSO) analysis, and univariate and multivariate Cox regression analysis were used for prognostic gene screening and prognostic model construction. The correlation of immune cell infiltration and risk scores was analyzed as well. Molecular docking was used to explore the relevance of related genes to anti-cancer drugs.Results: Ten ICD associated differentially expressed genes in HCC were found, and all of them had good predictive ability for HCC. ICD gene high amount of expression group was associated with poor prognosis (p = 0.015). The TME, immune cell infiltration and gene expression were different between ICD high and low groups (all p < 0.05). Six ICD associated genes (BAX, CASP8, IFNB1, LY96, NT5E and PIK3CA) which could predict the survival status were identified and used to construct the prognostic model for HCC. A risk score was calculated and it could be used as an independent prognostic factor in HCC patients (p < 0.001). In addition, the risk score had a positive correlation with macrophage M0 (r = 0.33, p = 0.0086). Molecular docking indicated that sorafenib could bind strongly to the target protein, representing that sorafenib may exert anticancer effects through these six ICD associated genes.Conclusion: This study established a prognostic model including six ICD associated genes for HCC, which may deepen our understanding of ICD and guide therapy for HCC patients.https://www.frontiersin.org/articles/10.3389/fphar.2023.1122011/fullhepatocellular carcinomaimmunogenic cell deathprognosistumor microenvironmentbioinformatics analysis |
| spellingShingle | Jiankang Xiang Chuan Liu Qingmin He Pengzhan He Weiguo Dong Comprehensive analysis of immunogenic cell death associated genes expression, tumor microenvironment, and prognosis in hepatocellular carcinoma Frontiers in Pharmacology hepatocellular carcinoma immunogenic cell death prognosis tumor microenvironment bioinformatics analysis |
| title | Comprehensive analysis of immunogenic cell death associated genes expression, tumor microenvironment, and prognosis in hepatocellular carcinoma |
| title_full | Comprehensive analysis of immunogenic cell death associated genes expression, tumor microenvironment, and prognosis in hepatocellular carcinoma |
| title_fullStr | Comprehensive analysis of immunogenic cell death associated genes expression, tumor microenvironment, and prognosis in hepatocellular carcinoma |
| title_full_unstemmed | Comprehensive analysis of immunogenic cell death associated genes expression, tumor microenvironment, and prognosis in hepatocellular carcinoma |
| title_short | Comprehensive analysis of immunogenic cell death associated genes expression, tumor microenvironment, and prognosis in hepatocellular carcinoma |
| title_sort | comprehensive analysis of immunogenic cell death associated genes expression tumor microenvironment and prognosis in hepatocellular carcinoma |
| topic | hepatocellular carcinoma immunogenic cell death prognosis tumor microenvironment bioinformatics analysis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1122011/full |
| work_keys_str_mv | AT jiankangxiang comprehensiveanalysisofimmunogeniccelldeathassociatedgenesexpressiontumormicroenvironmentandprognosisinhepatocellularcarcinoma AT chuanliu comprehensiveanalysisofimmunogeniccelldeathassociatedgenesexpressiontumormicroenvironmentandprognosisinhepatocellularcarcinoma AT qingminhe comprehensiveanalysisofimmunogeniccelldeathassociatedgenesexpressiontumormicroenvironmentandprognosisinhepatocellularcarcinoma AT pengzhanhe comprehensiveanalysisofimmunogeniccelldeathassociatedgenesexpressiontumormicroenvironmentandprognosisinhepatocellularcarcinoma AT weiguodong comprehensiveanalysisofimmunogeniccelldeathassociatedgenesexpressiontumormicroenvironmentandprognosisinhepatocellularcarcinoma |