Development and validation of a novel immune-related prognostic model in hepatocellular carcinoma
Abstract Background Growing evidence has suggested that immune-related genes play crucial roles in the development and progression of hepatocellular carcinoma (HCC). Nevertheless, the utility of immune-related genes for evaluating the prognosis of HCC patients are still lacking. The study aimed to e...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2020-02-01
|
| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-020-02255-6 |
| _version_ | 1819054807505174528 |
|---|---|
| author | Zheng Wang Jie Zhu Yongjuan Liu Changhong Liu Wenqi Wang Fengzhe Chen Lixian Ma |
| author_facet | Zheng Wang Jie Zhu Yongjuan Liu Changhong Liu Wenqi Wang Fengzhe Chen Lixian Ma |
| author_sort | Zheng Wang |
| collection | DOAJ |
| description | Abstract Background Growing evidence has suggested that immune-related genes play crucial roles in the development and progression of hepatocellular carcinoma (HCC). Nevertheless, the utility of immune-related genes for evaluating the prognosis of HCC patients are still lacking. The study aimed to explore gene signatures and prognostic values of immune-related genes in HCC. Methods We comprehensively integrated gene expression data acquired from 374 HCC and 50 normal tissues in The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) analysis and univariate Cox regression analysis were performed to identify DEGs that related to overall survival. An immune prognostic model was constructed using the Lasso and multivariate Cox regression analyses. Furthermore, Cox regression analysis was applied to identify independent prognostic factors in HCC. The correlation analysis between immune-related signature and immune cells infiltration were also investigated. Finally, the signature was validated in an external independent dataset. Results A total of 329 differentially expressed immune‐related genes were detected. 64 immune‐related genes were identified to be markedly related to overall survival in HCC patients using univariate Cox regression analysis. Then we established a TF-mediated network for exploring the regulatory mechanisms of these genes. Lasso and multivariate Cox regression analyses were applied to construct the immune-based prognostic model, which consisted of nine immune‐related genes. Further analysis indicated that this immune-related prognostic model could be an independent prognostic indicator after adjusting to other clinical factors. The relationships between the risk score model and immune cell infiltration suggested that the nine-gene signature could reflect the status of tumor immune microenvironment. The prognostic value of this nine-gene prognostic model was further successfully validated in an independent database. Conclusions Together, our study screened potential prognostic immune-related genes and established a novel immune-based prognostic model of HCC, which not only provides new potential prognostic biomarkers and therapeutic targets, but also deepens our understanding of tumor immune microenvironment status and lays a theoretical foundation for immunotherapy. |
| first_indexed | 2024-12-21T12:57:30Z |
| format | Article |
| id | doaj.art-39019402c0154560a0552279b5123eda |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-21T12:57:30Z |
| publishDate | 2020-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-39019402c0154560a0552279b5123eda2022-12-21T19:03:18ZengBMCJournal of Translational Medicine1479-58762020-02-0118111610.1186/s12967-020-02255-6Development and validation of a novel immune-related prognostic model in hepatocellular carcinomaZheng Wang0Jie Zhu1Yongjuan Liu2Changhong Liu3Wenqi Wang4Fengzhe Chen5Lixian Ma6Department of Infectious Diseases, Qilu Hospital, Shandong UniversityDepartment of Infectious Diseases, Qilu Hospital, Shandong UniversityShandong Center for Disease Control and Prevention, Health Education InstituteDepartment of Gastroenterology, Shandong Provincial Qianfoshan Hospital, The First Hospital Affiliated With Shandong First Medical UniversityDepartment of Gastroenterology, Shandong Provincial Qianfoshan Hospital, The First Hospital Affiliated With Shandong First Medical UniversityDepartment of Infectious Diseases, Qilu Hospital, Shandong UniversityDepartment of Infectious Diseases, Qilu Hospital, Shandong UniversityAbstract Background Growing evidence has suggested that immune-related genes play crucial roles in the development and progression of hepatocellular carcinoma (HCC). Nevertheless, the utility of immune-related genes for evaluating the prognosis of HCC patients are still lacking. The study aimed to explore gene signatures and prognostic values of immune-related genes in HCC. Methods We comprehensively integrated gene expression data acquired from 374 HCC and 50 normal tissues in The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) analysis and univariate Cox regression analysis were performed to identify DEGs that related to overall survival. An immune prognostic model was constructed using the Lasso and multivariate Cox regression analyses. Furthermore, Cox regression analysis was applied to identify independent prognostic factors in HCC. The correlation analysis between immune-related signature and immune cells infiltration were also investigated. Finally, the signature was validated in an external independent dataset. Results A total of 329 differentially expressed immune‐related genes were detected. 64 immune‐related genes were identified to be markedly related to overall survival in HCC patients using univariate Cox regression analysis. Then we established a TF-mediated network for exploring the regulatory mechanisms of these genes. Lasso and multivariate Cox regression analyses were applied to construct the immune-based prognostic model, which consisted of nine immune‐related genes. Further analysis indicated that this immune-related prognostic model could be an independent prognostic indicator after adjusting to other clinical factors. The relationships between the risk score model and immune cell infiltration suggested that the nine-gene signature could reflect the status of tumor immune microenvironment. The prognostic value of this nine-gene prognostic model was further successfully validated in an independent database. Conclusions Together, our study screened potential prognostic immune-related genes and established a novel immune-based prognostic model of HCC, which not only provides new potential prognostic biomarkers and therapeutic targets, but also deepens our understanding of tumor immune microenvironment status and lays a theoretical foundation for immunotherapy.https://doi.org/10.1186/s12967-020-02255-6Hepatocellular carcinomaImmune related genePrognosisPrognostic signatureBioinformatics |
| spellingShingle | Zheng Wang Jie Zhu Yongjuan Liu Changhong Liu Wenqi Wang Fengzhe Chen Lixian Ma Development and validation of a novel immune-related prognostic model in hepatocellular carcinoma Journal of Translational Medicine Hepatocellular carcinoma Immune related gene Prognosis Prognostic signature Bioinformatics |
| title | Development and validation of a novel immune-related prognostic model in hepatocellular carcinoma |
| title_full | Development and validation of a novel immune-related prognostic model in hepatocellular carcinoma |
| title_fullStr | Development and validation of a novel immune-related prognostic model in hepatocellular carcinoma |
| title_full_unstemmed | Development and validation of a novel immune-related prognostic model in hepatocellular carcinoma |
| title_short | Development and validation of a novel immune-related prognostic model in hepatocellular carcinoma |
| title_sort | development and validation of a novel immune related prognostic model in hepatocellular carcinoma |
| topic | Hepatocellular carcinoma Immune related gene Prognosis Prognostic signature Bioinformatics |
| url | https://doi.org/10.1186/s12967-020-02255-6 |
| work_keys_str_mv | AT zhengwang developmentandvalidationofanovelimmunerelatedprognosticmodelinhepatocellularcarcinoma AT jiezhu developmentandvalidationofanovelimmunerelatedprognosticmodelinhepatocellularcarcinoma AT yongjuanliu developmentandvalidationofanovelimmunerelatedprognosticmodelinhepatocellularcarcinoma AT changhongliu developmentandvalidationofanovelimmunerelatedprognosticmodelinhepatocellularcarcinoma AT wenqiwang developmentandvalidationofanovelimmunerelatedprognosticmodelinhepatocellularcarcinoma AT fengzhechen developmentandvalidationofanovelimmunerelatedprognosticmodelinhepatocellularcarcinoma AT lixianma developmentandvalidationofanovelimmunerelatedprognosticmodelinhepatocellularcarcinoma |