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整合单细胞和批量 RNA-seq 分析识别了结直肠癌中的预后 T 细胞特征

英文原题:Integrated single-cell and bulk RNA-seq analysis identifies a prognostic T-cell signature in colorectal cancer.

查看英文原题

Integrated single-cell and bulk RNA-seq analysis identifies a prognostic T-cell signature in colorectal cancer.

PubMed 2024/08/30(内容时间) Sci Rep Q1 · IF 4.9(JCR 2025)

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中文摘要

结直肠癌(CRC)是全球发病率和死亡率的主要原因,需要更有效的治疗方法。T细胞在肿瘤微环境中占主导地位,在调节CRC的免疫治疗反应和临床结局中发挥关键作用。

本研究引入了一种利用单细胞测序数据表征CRC免疫微环境的开创性方法。与以往聚焦于单个T细胞特征基因的方法不同,我们利用了结直肠癌特征性T细胞的整体浸润水平。通过加权基因共表达网络分析、Lasso回归和StepCox分析,我们基于六个T细胞相关基因开发了一个预后风险模型TRGS(T细胞相关基因特征)。多因素Cox分析确定TRGS是CRC的独立预后因素,其预测效能优于现有的免疫相关预后模型。免疫反应性分析显示,低风险组的Immunophenoscore更高,Tumor Immune Dysfunction and Exclusion评分更低,表明对免疫检查点抑制剂治疗可能具有应答性。

此外,低风险组患者对基于5-氟尿嘧啶的化疗方案表现出更高的敏感性。总之,TRGS作为CRC的独立预后生物标志物,为优化患者对免疫治疗和化疗的应答提供了见解,从而为个性化肿瘤管理策略奠定了基础。

展开英文摘要原文

Colorectal cancer (CRC) is a major contributor to global morbidity and mortality, necessitating more effective therapeutic approaches. T cells, prominent in the tumor microenvironment, exert a crucial role in modulating immunotherapeutic responses and clinical outcomes in CRC.

This study introduces a pioneering method for characterizing the CRC immune microenvironment using single-cell sequencing data. Unlike previous approaches, which focused on individual T-cell signature genes, we utilized overall infiltration levels of colorectal cancer signature T-cells. Through weighted gene co-expression network analysis, Lasso regression, and StepCox analysis, we developed a prognostic risk model, TRGS (T-cell related genes signatures), based on six T cell-related genes.

Multivariate Cox analysis identified TRGS as an independent prognostic factor for CRC, showcasing its superior predictive efficacy compared to existing immune-related prognostic models. Immunoreactivity analysis revealed higher Immunophenoscore and lower Tumor Immune Dysfunction and Exclusion scores in the low-risk group, indicating potential responsiveness to immune checkpoint inhibitor therapy.

Additionally, patients in the low-risk group demonstrated heightened sensitivity to 5-fluorouracil-based chemotherapy regimens. In summary, TRGS emerges as a standalone prognostic biomarker for CRC, offering insights to optimize patient responses to immunotherapy and chemotherapy, thereby laying the groundwork for personalized tumor management strategies.

论文信息

作者
Cui P、Wang H、Bai Z
第一作者单位
Department of General Surgery, State Key Lab of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, People's Republic of China.China
通讯作者单位
Department of General Surgery, State Key Lab of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, People's Republic of China. baizhigang@ccmu.edu.cn.China
期刊
Scientific reports2024 Aug 30
原文标识
PubMed 39215032 · DOI 10.1038/s41598-024-70422-6