Identification and Validation of Immune-Related Gene Prognostic Signature for Hepatocellular Carcinoma

Immune-related genes (IRGs) have been identified as critical drivers of the initiation and progression of hepatocellular carcinoma (HCC). This study is aimed at constructing an IRG signature for HCC and validating its prognostic value in clinical application. The prognostic signature was developed b...

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Main Authors: Wenbiao Chen, Minglin Ou, Donge Tang, Yong Dai, Weibo Du
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2020/5494858
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author Wenbiao Chen
Minglin Ou
Donge Tang
Yong Dai
Weibo Du
author_facet Wenbiao Chen
Minglin Ou
Donge Tang
Yong Dai
Weibo Du
author_sort Wenbiao Chen
collection DOAJ
description Immune-related genes (IRGs) have been identified as critical drivers of the initiation and progression of hepatocellular carcinoma (HCC). This study is aimed at constructing an IRG signature for HCC and validating its prognostic value in clinical application. The prognostic signature was developed by integrating multiple IRG expression data sets from TCGA and GEO databases. The IRGs were then combined with clinical features to validate the robustness of the prognostic signature through bioinformatics tools. A total of 1039 IRGs were identified in the 657 HCC samples. Subsequently, the IRGs were subjected to univariate Cox regression and LASSO Cox regression analyses in the training set to construct an IRG signature comprising nine immune-related gene pairs (IRGPs). Functional analyses revealed that the nine IRGPs were associated with tumor immune mechanisms, including cell proliferation, cell-mediated immunity, and tumorigenesis signal pathway. Concerning the overall survival rate, the IRGPs distinctly grouped the HCC samples into the high- and low-risk groups. Also, we found that the risk score based on nine IRGPs was related to clinical and pathologic factors and remained a valid independent prognostic signature after adjusting for tumor TNM, grade, and grade in multivariate Cox regression analyses. The prognostic value of the nine IRGPs was further validated by forest and nomogram plots, which revealed that it was superior to the tumor TNM, grade, and stage. Our findings suggest that the nine-IRGP signature can be effective in determining the disease outcomes of HCC patients.
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spelling doaj-art-73e351e678f54f158ce07141aea8ea262025-08-20T02:06:47ZengWileyJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/54948585494858Identification and Validation of Immune-Related Gene Prognostic Signature for Hepatocellular CarcinomaWenbiao Chen0Minglin Ou1Donge Tang2Yong Dai3Weibo Du4State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, ChinaScientific Research Center, The Second Affiliated Hospital of Guilin Medical University, Guilin 541199, ChinaClinical Medical Research Center of The Second Clinical Medical College, Jinan University, Shenzhen People’s Hospital, No. 1017, Dongmen North Road, Luohu District, Shenzhen 518020, ChinaClinical Medical Research Center of The Second Clinical Medical College, Jinan University, Shenzhen People’s Hospital, No. 1017, Dongmen North Road, Luohu District, Shenzhen 518020, ChinaState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, ChinaImmune-related genes (IRGs) have been identified as critical drivers of the initiation and progression of hepatocellular carcinoma (HCC). This study is aimed at constructing an IRG signature for HCC and validating its prognostic value in clinical application. The prognostic signature was developed by integrating multiple IRG expression data sets from TCGA and GEO databases. The IRGs were then combined with clinical features to validate the robustness of the prognostic signature through bioinformatics tools. A total of 1039 IRGs were identified in the 657 HCC samples. Subsequently, the IRGs were subjected to univariate Cox regression and LASSO Cox regression analyses in the training set to construct an IRG signature comprising nine immune-related gene pairs (IRGPs). Functional analyses revealed that the nine IRGPs were associated with tumor immune mechanisms, including cell proliferation, cell-mediated immunity, and tumorigenesis signal pathway. Concerning the overall survival rate, the IRGPs distinctly grouped the HCC samples into the high- and low-risk groups. Also, we found that the risk score based on nine IRGPs was related to clinical and pathologic factors and remained a valid independent prognostic signature after adjusting for tumor TNM, grade, and grade in multivariate Cox regression analyses. The prognostic value of the nine IRGPs was further validated by forest and nomogram plots, which revealed that it was superior to the tumor TNM, grade, and stage. Our findings suggest that the nine-IRGP signature can be effective in determining the disease outcomes of HCC patients.http://dx.doi.org/10.1155/2020/5494858
spellingShingle Wenbiao Chen
Minglin Ou
Donge Tang
Yong Dai
Weibo Du
Identification and Validation of Immune-Related Gene Prognostic Signature for Hepatocellular Carcinoma
Journal of Immunology Research
title Identification and Validation of Immune-Related Gene Prognostic Signature for Hepatocellular Carcinoma
title_full Identification and Validation of Immune-Related Gene Prognostic Signature for Hepatocellular Carcinoma
title_fullStr Identification and Validation of Immune-Related Gene Prognostic Signature for Hepatocellular Carcinoma
title_full_unstemmed Identification and Validation of Immune-Related Gene Prognostic Signature for Hepatocellular Carcinoma
title_short Identification and Validation of Immune-Related Gene Prognostic Signature for Hepatocellular Carcinoma
title_sort identification and validation of immune related gene prognostic signature for hepatocellular carcinoma
url http://dx.doi.org/10.1155/2020/5494858
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AT dongetang identificationandvalidationofimmunerelatedgeneprognosticsignatureforhepatocellularcarcinoma
AT yongdai identificationandvalidationofimmunerelatedgeneprognosticsignatureforhepatocellularcarcinoma
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