基于生物信息学分析鉴定胃腺癌中与 NOTCH1 相关的 8 基因风险预测特征

英文原题：Identification of 8-gene risk prediction signature associated with NOTCH1 in stomach adenocarcinoma based on bioinformatics analysis.

PubMed 2022/08/01（内容时间） J Gastrointest Oncol Q3 · IF 2.1（JCR 2025）

技术：γδ T 细胞胃癌地区：中国

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研究概要

NOTCH1 可能是胃腺癌的潜在靶点。

中文摘要

背景：胃腺癌（STAD）是最常见的胃癌组织学类型，死亡率高、预后较差。本研究探讨Notch受体1（NOTCH1）对STAD免疫微环境的影响。方法：比较STAD队列中的免疫细胞特征，并分析NOTCH1基因与肿瘤免疫细胞浸润的相关性，鉴定与NOTCH1相关的免疫基因（IRG）。基于这些NOTCH1相关IRG建立多基因风险预测特征；通过单变量分析评估入选IRG表达与总生存期（OS）的关系，并依据各基因表达及其权重计算风险评分。研究还构建预后列线图，用于预测个体生存概率。结果：在STAD中，NOTCH1表达与TIL（肿瘤浸润淋巴细胞）中的活化树突状细胞（DC）（r=-0.196，p=6.24×10⁻⁵）、CD56bright细胞（r=-0.115，p=0.0193）、未成熟DC（r=-0.293，p=1.16×10⁻⁹）、单核细胞（r=-0.185，p=0.000149）、中央记忆CD4 T细胞（r=-0.126，p=0.0103）及γδT细胞（r=-0.149，p=0.00229）均呈显著负相关。由8个基因构成的风险预测特征中，CRHR2、FLT1、FLT4、GFAP、PDGFRB、PTGDR、SEMA5B和TYK2均为STAD患者的独立预后预测因子，其风险比依次为1.858、1.268、1.334、2.739、1.192、1.564、1.154和0.734（均有统计学意义，p值为0.008–0.049）。结论：NOTCH1可能是STAD的潜在治疗靶点。NOTCH1介导的免疫特征如何影响预后，仍需进一步研究。

展开英文摘要原文

BACKGROUND: Stomach adenocarcinoma (STAD), is the most common histological type of gastric cancer (GC) with high mortality and poor prognosis. We sought to investigate the contribution of Notch receptor 1 ( NOTCH1 ) to STAD immunity. METHODS: The profiles of immune cells in STAD cohorts were compared, and a correlation analysis between the NOTCH1 gene and tumor immune cell infiltration was then conducted. The immune-related genes (IRGs) associated with the NOTCH1 gene were identified. Based on the NOTCH1 -associated IRGs, multiple-gene risk prediction signatures were established. The relationship between the expression levels of the selected IRGs and overall survival (OS) was analyzed by a univariate analysis. The risk score was calculated using the formula of 1 x 1 + 2 x 2 +... + ixi . A prognostic nomogram was constructed to predict individuals' survival probabilities. RESULTS: In STAD, NOTCH1 expression levels were significantly negatively associated with tumor-infiltrating lymphocyte (TIL) Act dendritic cells (DCs) (r=-0.196, P value =6.24e-05), TIL cluster of differentiation (CD) 56 bright cells (r=-0.115, P value =0.0193), TIL immature DCs (r=-0.293, P value =1.16e-09), TIL monocyte cells (r=-0.185, P value =0.000149), TIL central memory T CD4 cells (r=-0.126, P value =0.0103), and TIL gamma delta T cells (r=-0.149, P value =0.00229). The resulting risk scores of the 8-gene risk prediction signature (corticotrophin releasing hormone receptor 2 ( CRHR2 ) (HR =1.858, P value =0.048), fms related receptor tyrosine kinase 1 ( FLT1 ) (HR =1.268, P value =0.048), fms related receptor tyrosine kinase 4 ( FLT4 ) (HR =1.334, P value =0.031), glial fibrillary acidic protein ( GFAP ) (HR =2.739, P value =0.008), platelet-derived growth factor receptor beta ( PDGFRB ) (HR =1.192, P value =0.02), prostaglandin D2 receptor ( PTGDR ) (HR =1.564, P value =0.049), semaphorin 5B ( SEMA5B ) (HR =1.154, P value =0.029), and tyrosine kinase 2 ( TYK2 ) (HR =0.734, P value =0.041) were independent prognostic predictors for STAD patients. CONCLUSIONS: NOTCH1 could be a potential target for STAD. The mechanisms underpinning NOTCH1 -medicated prognostic values of immune signatures should be further explored.

论文信息

作者: Pan D、Lin C、Lin X、Li L
单位: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.China
期刊: Journal of gastrointestinal oncology2022 Aug

原文标识: PubMed 36092350　·　DOI 10.21037/jgo-22-685

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