间皮素作为癌症免疫治疗的生物标志物和治疗靶点
Mesothelin as Biomarker and Therapeutic Target for Immunotherapy in Cancer.
癌症仍是一个关键的全球健康问题,原因在于发现晚、耐药和高死亡率。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Profiling the Tumor-Infiltrating Lymphocytes in Gastric Cancer Reveals Its Implication in the Prognosis.
Profiling the Tumor-Infiltrating Lymphocytes in Gastric Cancer Reveals Its Implication in the Prognosis.
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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。
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.
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