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胃癌 TIL(肿瘤浸润淋巴细胞)图谱分析揭示其预后意义

英文原题:Profiling the Tumor-Infiltrating Lymphocytes in Gastric Cancer Reveals Its Implication in the Prognosis.

查看英文原题

Profiling the Tumor-Infiltrating Lymphocytes in Gastric Cancer Reveals Its Implication in the Prognosis.

PubMed 2022/06/05(内容时间) Genes (Basel) Q2 · IF 3.1(JCR 2025)

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中文摘要

胃癌是全球第五常见恶性肿瘤,也是癌症相关死亡的第三大原因。免疫疗法为胃癌患者提供了有前景的新治疗选择,但仅对少数患者有效。

本研究采用去卷积方法分析公开的肿瘤整体RNA测序数据,评估TCGA胃腺癌(STAD)队列中22种TIL(肿瘤浸润淋巴细胞)的组成。根据免疫细胞谱和预后结果将患者分为高TIL和低TIL亚型。研究鉴定了两亚型间差异表达基因(DEG);GO/KEGG分析显示,PD-L1和PD-1等多种免疫基因在高TIL亚型中高表达。研究构建以DEG为核心的综合蛋白质互作(PPI)网络,并进一步识别16个枢纽基因。基于这些枢纽基因,研究建立含11个基因特征的弹性模型(NKG7、GZMB、IL2RB、CCL5、CD8A、IDO1、MYH1、GNLY、CXCL11、GBP5和PRF1),用于预测高TIL亚型。

总之,胃癌患者肿瘤免疫微环境中的TIL组成高度异质,TIL特征有望成为预测患者治疗应答和总生存期结局的标志物。

展开英文摘要原文

Gastric cancer is the fifth most common malignancy and the third leading cause of cancer-related mortality worldwide. Immunotherapy offers promising new treatment options for gastric cancer patients; however, it is only effective in a limited fraction of patients. In this study, we evaluated the composition of 22 tumor-infiltrating lymphocytes (TILs) in TCGA Stomach Adenocarcinoma (STAD) using deconvolution-based method by analyzing the publicly available bulk tumor RNA-seq data. The patients were classified into high-TIL and low-TIL subtypes based on their immune cell profiles and prognosis outputs. The differentially expressed genes (DEGs) between the two subtypes were identified, and GO/KEGG analysis showed that broad immune genes, such as PD-L1 and PD-1, were highly expressed in the high-TIL subtype.

A comprehensive protein-protein interaction (PPI) network centered on DEGs was built, and 16 hub genes of the network were further identified. Based on the hub genes, an elastic model with 11 gene signatures ( NKG7 , GZMB , IL2RB , CCL5 , CD8A , IDO1 , MYH1 , GNLY , CXCL11 , GBP5 and PRF1 ) was developed to predict the high-TIL subtype.

In summary, our findings showed that the compositions of TILs within the tumor immune microenvironment of stomach cancer patients are highly heterogeneous, and the profiles of TILs have the potential to be predictive markers of patients' responses and overall survival outcomes.

论文信息

作者
Yu W、Wang S、Rong Q、Ajayi OE、Hu K、Wu Q
单位
Division of Molecular Medicine, CAS Key Laboratory of Innate Immunity and Chronic Disease, Department of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China.China
文献类型
非美国政府资助研究
期刊
Genes2022 Jun 5
原文标识
PubMed 35741779 · DOI 10.3390/genes13061017