T-cell exhaustion signatures characterize the immune landscape and predict HCC prognosis via integrating single-cell RNA-seq and bulk RNA-sequencing

作者全名："Chi, Hao; Zhao, Songyun; Yang, Jinyan; Gao, Xinrui; Peng, Gaoge; Zhang, Jinhao; Xie, Xixi; Song, Guobin; Xu, Ke; Xia, Zhijia; Chen, Shi; Zhao, Jinqiu"

作者地址："[Chi, Hao; Gao, Xinrui; Peng, Gaoge] Southwest Med Univ, Clin Med Coll, Luzhou, Peoples R China; [Zhao, Songyun] Nanjing Med Univ, Wuxi Peoples Hosp, Dept Neurosurg, Wuxi, Peoples R China; [Yang, Jinyan; Zhang, Jinhao; Xie, Xixi; Song, Guobin] Southwest Med Univ, Sch Stomatol, Luzhou, Peoples R China; [Xu, Ke] Chongqing Gen Hosp, Dept Oncol, Chongqing, Peoples R China; [Xia, Zhijia] Ludwig Maximilians Univ Munchen, Dept Gen Visceral & Transplant Surg, Munich, Germany; [Chen, Shi] Chongqing Med Univ, Affiliated Hosp 1, Clin Mol Med Testing Ctr, Chongqing, Peoples R China; [Zhao, Jinqiu] Chongqing Med Univ, Affiliated Hosp 1, Dept Infect Dis, Chongqing, Peoples R China"

通信作者："Xia, ZJ (通讯作者)，Ludwig Maximilians Univ Munchen, Dept Gen Visceral & Transplant Surg, Munich, Germany.; Chen, S (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Clin Mol Med Testing Ctr, Chongqing, Peoples R China.; Zhao, JQ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Infect Dis, Chongqing, Peoples R China."

来源：FRONTIERS IN IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000955490600001

JCR分区：Q1

影响因子：7.3

年份：2023

卷号：14

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：T-cell exhaustion; HCC; single-cell RNA-seq; machine learning; tumor microenvironment; immunotherapy; predictive signature

摘要："BackgroundHepatocellular carcinoma (HCC), the third most prevalent cause of cancer-related death, is a frequent primary liver cancer with a high rate of morbidity and mortality. T-cell depletion (TEX) is a progressive decline in T-cell function due to continuous stimulation of the TCR in the presence of sustained antigen exposure. Numerous studies have shown that TEX plays an essential role in the antitumor immune process and is significantly associated with patient prognosis. Hence, it is important to gain insight into the potential role of T cell depletion in the tumor microenvironment. The purpose of this study was to develop a trustworthy TEX-based signature using single-cell RNA-seq (scRNA-seq) and high-throughput RNA sequencing, opening up new avenues for evaluating the prognosis and immunotherapeutic response of HCC patients. MethodsThe International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) databases were used to download RNA-seq information for HCC patients. The 10x scRNA-seq. data of HCC were downloaded from GSE166635, and UMAP was used for clustering descending, and subgroup identification. TEX-related genes were identified by gene set variance analysis (GSVA) and weighted gene correlation network analysis (WGCNA). Afterward, we established a prognostic TEX signature using LASSO-Cox analysis. External validation was performed in the ICGC cohort. Immunotherapy response was assessed by the IMvigor210, GSE78220, GSE79671, and GSE91061cohorts. In addition, differences in mutational landscape and chemotherapy sensitivity between different risk groups were investigated. Finally, the differential expression of TEX genes was verified by qRT-PCR. Result11 TEX genes were thought to be highly predictive of the prognosis of HCC and substantially related to HCC prognosis. Patients in the low-risk group had a greater overall survival rate than those in the high-risk group, according to multivariate analysis, which also revealed that the model was an independent predictor of HCC. The predictive efficacy of columnar maps created from clinical features and risk scores was strong. ConclusionTEX signature and column line plots showed good predictive performance, providing a new perspective for assessing pre-immune efficacy, which will be useful for future precision immuno-oncology studies."

基金机构："National Natural Science Foundation of China [82100656]; China Postdoctoral Science Foundation [2022M710563]; Science and Technology Joint Medical Foundation of Chongqing, China [2020FYYX008]"

基金资助正文："Funding This study was funded by the National Natural Science Foundation of China (Grant NO.82100656), China Postdoctoral Science Foundation(2022M710563), and Science and Technology Joint Medical Foundation of Chongqing, China (Grant NO. 2020FYYX008)."