首页|A Novel mRNA Signature Related to Immunity to Predict Survival and Immunotherapy Response in Hepatocellular Carcinoma

A Novel mRNA Signature Related to Immunity to Predict Survival and Immunotherapy Response in Hepatocellular Carcinoma

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Background and Aims: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the incidence and mortality rates are increasing. Given the limited treat-ments of HCC and promising application of immunotherapy for cancer, we aimed to identify an immune-related prog-nostic signature that can predict overall survival (OS) rates and immunotherapy response in HCC. Methods: The initial signature development was conducted using a training data-set from the Cancer Genome Atlas followed by independent internal and external validations from that resource and the Gene Expression Omnibus. A signature based nomogram was generated using multivariate Cox regression analysis. The associations of signature score with tumor immune phenotype and response to immunotherapy were analyzed using single-sample gene set enrichment analysis and tu-mor immune dysfunction and exclusion algorithm. A cohort from Zhongshan Hospital was employed to verify the pre- dictive robustness of the signature regarding prognostic risk and immunotherapy response. Results: The prognostic sig-nature, IGSHCC, consisting of 22 immune-related genes, had independent prognostic ability, with training and validation cohorts. Also, IGSHCC stratified HCC patients with different outcomes in subgroups. The prognostic accuracy of IGSHCC was better than three reported prognostic signatures. The IGSHCC-based nomogram had high accuracy and significant clinical benefits in predicting 3- and 5-year OS. IGSHCC re-flected distinct immunosuppressive phenotypes in low- and high-score groups. Patients with low IGSHCC scores were more likely than those with high scores to benefit from im-munotherapy. Conclusions: IGSHCC predicted HCC prog-nosis and response to immunotherapy, and contributed to individualized clinical management.

Hepatocellular carcinomaGene signatureImmune microenviron-mentPrognosisImmunotherapy

Chenhao Zhou、Jialei Weng、Yuan Gao、Chunxiao Liu、Xiaoqiang Zhu、Qiang Zhou、Chia-Wei Li、Jialei Sun、Manar Atyah、Yong Yi、Qinghai Ye、Yi Shi、Qiongzhu Dong、Yingbin Liu、Mien-Chie Hung、Ning Ren

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Department of Liver Surgery,Liver Cancer Institute,Zhongshan Hospital,and Key Laboratory of Carcinogenesis andCancer Invasion(Ministry of Education),Fudan University,Shanghai,China

Department of Molecular and Cellular Oncol-ogy,The University of Texas MD Anderson Cancer Center,Houston,TX,USA

Department of Biliary-Pancreatic Surgery,Renji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai,China

School of Biomedical Sciences,Li Ka Shing Faculty of Medicine,The University of Hong Kong,Pok Fu Lam,Hong Kong SAR,China

Biomedical Research Center,Zhongshan Hospital,Fudan University,Shanghai,China

Institute of Fudan Minhang Academic Health System,and KeyLaboratory of Whole-period Monitoring and Precise Intervention of Digestive Cancer(SMHC),Minhang Hospital&AHS,Fudan University,Shanghai,China

Institutes of Biomedical Sciences,Fudan University,Shanghai,China

Graduate Insti-tute of Biomedical Sciences and Center for Molecular Medicine,China Medical University,Taichung

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国家自然科学基金国家自然科学基金Shanghai Sailing Program中国博士后科学基金Special Foundation for Science and Technology Basic Research ProgramShanghai Shen Kang Hospital Development Center new frontier technology joint project

821035218207320821YF14075002021M6906742019FY101103SHDC12021109

2022

10.14218/JCTH.2021.00283

临床与转化肝病杂志(英文版)

临床与转化肝病杂志(英文版)

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年,卷(期)：2022.10(5)
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