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.

IF 3.2 4区 医学 Q3 IMMUNOLOGY Journal of Immunotherapy Pub Date : 2024-09-01 Epub Date: 2024-05-29 DOI:10.1097/CJI.0000000000000528
Zhi-Gang Zhu, Zheng Wang, Qiong Wu, Dong-Liu Miao, Yi-Qi Jin, Lei Chen
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Abstract

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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基于批量和单细胞 RNA 测序数据的综合分析,确定预测胃癌预后的 CD8+ T 细胞相关特征。
肿瘤微环境中的 CD8+ T 细胞浸润与更好的生存和免疫治疗反应有关。然而,迄今为止,它们在胃癌中的作用尚未得到探讨。本文从癌症基因组图谱数据库中收集了胃癌基因表达谱。单细胞转录组数据来自 GSE134520。细胞聚类、注释和CD8+ T细胞差异基因来自TISCH数据库。我们通过 scRNA-seq 分析确定了 896 个 CD8+ T 细胞差异基因。整合免疫相关基因后,得到了174个重叠基因,随后建立了一个新的风险模型。在训练集和外部验证集中评估了 CD8+ T 细胞相关基因特征的性能。基因特征显示了GC总生存率的独立风险因素。建立的定量提名图提高了该特征的临床疗效。此外,低风险个体表现出更高的突变状态、更高的免疫检查点表达、较低的肿瘤免疫功能障碍和排斥(TIDE)评分以及更高的IPS-PD-1联合IPS-CTLA4评分,这表明他们对免疫疗法的反应更大。此外,对IMvigor210免疫疗法队列的分析表明,低风险个体对预后和免疫疗法的反应良好。总之,我们生成的 CD8+ T 细胞相关特征可作为一种有前途的工具,用于 GC 患者的个性化预后预测和免疫治疗决策指导。
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来源期刊
Journal of Immunotherapy
Journal of Immunotherapy 医学-免疫学
CiteScore
6.90
自引率
0.00%
发文量
79
审稿时长
6-12 weeks
期刊介绍: Journal of Immunotherapy features rapid publication of articles on immunomodulators, lymphokines, antibodies, cells, and cell products in cancer biology and therapy. Laboratory and preclinical studies, as well as investigative clinical reports, are presented. The journal emphasizes basic mechanisms and methods for the rapid transfer of technology from the laboratory to the clinic. JIT contains full-length articles, review articles, and short communications.
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