Identification of the CD8+ T-cell Related Signature for Predicting the Prognosis of Gastric Cancer Based on Integrated Analysis of Bulk and Single-cell RNA Sequencing Data

免疫疗法 基因签名 列线图 CD8型 免疫系统 转录组 癌症免疫疗法 医学 癌症 肿瘤科 生物 基因 计算生物学 免疫学 基因表达 内科学 遗传学
作者
Zhigang Zhu,Zheng Wang,Qiong Wu,Dong-liu Miao,Yi-qi Jin,Lei Chen
出处
期刊:Journal of Immunotherapy [Ovid Technologies (Wolters Kluwer)]
卷期号:47 (7): 239-248 被引量:2
标识
DOI:10.1097/cji.0000000000000528
摘要

The infiltration of CD8 + T cells in the tumor microenvironment is associated with better survival and immunotherapy response. However, their roles in gastric cancer have not been explored so far. In here, the profiles of GC gene expression were collected from The Cancer Genome Atlas database. Single-cell transcriptomic data originated from GSE134520. Cell clustering, annotation, and CD8 + T-cell differential genes were from the TISCH database. We determined 896 CD8 + T-cell differential genes by scRNA-seq analysis. After integrating immune-related genes, 174 overlapping genes were obtained and a novel risk model was subsequently built. The performance of CD8 + T-cell–associated gene signature was assessed in the training and external validation sets. The gene signature showed independent risk factors of overall survival for GC. A quantitative nomogram was built to enhance the clinical efficacy of this signature. Furthermore, low-risk individuals showed higher mutation status, higher immune checkpoint expression, low Tumour Immune Dysfunction and Exclusion (TIDE) scores, and higher IPS-PD-1 combined IPS-CTLA4 scores, indicating a greater response to immunotherapy. In addition, analysis of IMvigor210 immunotherapy cohort demonstrated that low-risk individuals had a favorable response to prognosis and immunotherapy. In conclusion, we generated a CD8 + T-cell–related signature that can serve as a promising tool for personalized prognosis prediction and guiding decisions regarding immunotherapy in GC patients.
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