A Glycolysis-Related Gene Signature Correlates With the Characteristics of the Tumor Immune Microenvironment and Predicts Prognosis in Patients With Hepatocellular Carcinoma

Aim: To develop a glycolysis-related gene signature that correlated with the characteristics of the tumor immune microenvironment and had good predictive power for overall survival (OS) in hepatocellular carcinoma (HCC).Methods: Gene expression profiles, RNA sequencing data, clinical characteristics...

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Main Authors: Jun Yang, Yuening Zhang, Jin Duan, Xiaojie Huang, Haibin Yu, Zhongjie Hu
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-04-01
Series:Frontiers in Molecular Biosciences
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2022.834976/full
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author Jun Yang
Yuening Zhang
Jin Duan
Xiaojie Huang
Haibin Yu
Zhongjie Hu
author_facet Jun Yang
Yuening Zhang
Jin Duan
Xiaojie Huang
Haibin Yu
Zhongjie Hu
author_sort Jun Yang
collection DOAJ
description Aim: To develop a glycolysis-related gene signature that correlated with the characteristics of the tumor immune microenvironment and had good predictive power for overall survival (OS) in hepatocellular carcinoma (HCC).Methods: Gene expression profiles, RNA sequencing data, clinical characteristics and survival information for 407 patients with HCC and 58 healthy controls were downloaded from the TCGA database. GSEA 4.1.0 software was used to evaluate the glycolysis-related pathways enriched in HCC compared to normal liver tissue. Univariate Cox, Least Absolute Shrinkage, Selection Operator, and two-step multivariate Cox analyses were used to construct a glycolysis-related gene signature for prognostic prediction. The glycolysis-related gene signature was combined with clinical characteristics to generate a nomogram. Tumor-infiltrating immune cell profiles and PD-L1 protein expression in HCC tissues were investigated.Results: The gene expression profiles of HCC tissues were enriched in glycolysis-related pathways. A glycolysis-related gene signature was used to categorize patients as high-risk or low-risk, where high-risk patients had significantly worse OS. Receiver operating characteristic curves confirmed the predictive capability of the glycolysis-related gene signature for OS (AUC >0.80). There was a significant difference in M0 macrophage (p = 0.017), dendritic cell (p = 0.043), B cell (p = 0.0018), CD4 T cell (p = 0.003), Treg (p = 0.01) and mast cell (p = 0.02) content and PD-L1 protein expression (p = 0.019) between HCC tissues in patients in the high-risk and low-risk groups.Conclusion: We established a glycolysis-related gene signature for OS in HCC that was predictive in training and test TCGA cohorts and correlated with the characteristics of the HCC tumor immune microenvironment. The glycolysis-related gene signature may guide clinical decision-making concerning patient selection for immunotherapy in HCC.
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spelling doaj.art-dd69b3ec521940f4bc17e38ffd9402c22022-12-22T00:14:36ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-04-01910.3389/fmolb.2022.834976834976A Glycolysis-Related Gene Signature Correlates With the Characteristics of the Tumor Immune Microenvironment and Predicts Prognosis in Patients With Hepatocellular CarcinomaJun Yang0Yuening Zhang1Jin Duan2Xiaojie Huang3Haibin Yu4Zhongjie Hu5Phase Ⅰ Clinical Trial Ward, Beijing Youan Hospital, Capital Medical University, Beijing, ChinaBeijing Youan Hospital, Capital Medical University, Beijing, ChinaPhase Ⅰ Clinical Trial Ward, Beijing Youan Hospital, Capital Medical University, Beijing, ChinaBeijing Youan Hospital, Capital Medical University, Beijing, ChinaPhase Ⅰ Clinical Trial Ward, Beijing Youan Hospital, Capital Medical University, Beijing, ChinaBeijing Youan Hospital, Capital Medical University, Beijing, ChinaAim: To develop a glycolysis-related gene signature that correlated with the characteristics of the tumor immune microenvironment and had good predictive power for overall survival (OS) in hepatocellular carcinoma (HCC).Methods: Gene expression profiles, RNA sequencing data, clinical characteristics and survival information for 407 patients with HCC and 58 healthy controls were downloaded from the TCGA database. GSEA 4.1.0 software was used to evaluate the glycolysis-related pathways enriched in HCC compared to normal liver tissue. Univariate Cox, Least Absolute Shrinkage, Selection Operator, and two-step multivariate Cox analyses were used to construct a glycolysis-related gene signature for prognostic prediction. The glycolysis-related gene signature was combined with clinical characteristics to generate a nomogram. Tumor-infiltrating immune cell profiles and PD-L1 protein expression in HCC tissues were investigated.Results: The gene expression profiles of HCC tissues were enriched in glycolysis-related pathways. A glycolysis-related gene signature was used to categorize patients as high-risk or low-risk, where high-risk patients had significantly worse OS. Receiver operating characteristic curves confirmed the predictive capability of the glycolysis-related gene signature for OS (AUC >0.80). There was a significant difference in M0 macrophage (p = 0.017), dendritic cell (p = 0.043), B cell (p = 0.0018), CD4 T cell (p = 0.003), Treg (p = 0.01) and mast cell (p = 0.02) content and PD-L1 protein expression (p = 0.019) between HCC tissues in patients in the high-risk and low-risk groups.Conclusion: We established a glycolysis-related gene signature for OS in HCC that was predictive in training and test TCGA cohorts and correlated with the characteristics of the HCC tumor immune microenvironment. The glycolysis-related gene signature may guide clinical decision-making concerning patient selection for immunotherapy in HCC.https://www.frontiersin.org/articles/10.3389/fmolb.2022.834976/fullimmune-related glycolysis genehepatocellular carcinomaprognosisimmune microenvironmentPD-L1
spellingShingle Jun Yang
Yuening Zhang
Jin Duan
Xiaojie Huang
Haibin Yu
Zhongjie Hu
A Glycolysis-Related Gene Signature Correlates With the Characteristics of the Tumor Immune Microenvironment and Predicts Prognosis in Patients With Hepatocellular Carcinoma
Frontiers in Molecular Biosciences
immune-related glycolysis gene
hepatocellular carcinoma
prognosis
immune microenvironment
PD-L1
title A Glycolysis-Related Gene Signature Correlates With the Characteristics of the Tumor Immune Microenvironment and Predicts Prognosis in Patients With Hepatocellular Carcinoma
title_full A Glycolysis-Related Gene Signature Correlates With the Characteristics of the Tumor Immune Microenvironment and Predicts Prognosis in Patients With Hepatocellular Carcinoma
title_fullStr A Glycolysis-Related Gene Signature Correlates With the Characteristics of the Tumor Immune Microenvironment and Predicts Prognosis in Patients With Hepatocellular Carcinoma
title_full_unstemmed A Glycolysis-Related Gene Signature Correlates With the Characteristics of the Tumor Immune Microenvironment and Predicts Prognosis in Patients With Hepatocellular Carcinoma
title_short A Glycolysis-Related Gene Signature Correlates With the Characteristics of the Tumor Immune Microenvironment and Predicts Prognosis in Patients With Hepatocellular Carcinoma
title_sort glycolysis related gene signature correlates with the characteristics of the tumor immune microenvironment and predicts prognosis in patients with hepatocellular carcinoma
topic immune-related glycolysis gene
hepatocellular carcinoma
prognosis
immune microenvironment
PD-L1
url https://www.frontiersin.org/articles/10.3389/fmolb.2022.834976/full
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