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[摘要]
目的:筛选影响胃癌患者预后及治疗的关键基因,分析关键基因微纤维相关蛋白2(MFAP2)在提示胃癌患者预后及免 疫治疗敏感性中的价值。方法:从TCGA数据库下载胃癌患者的癌和癌旁组织的表达谱数据及临床资料。综合加权基因共表达 网络分析(WGCNA)和单因素Cox回归分析筛选与胃癌预后显著相关的基因。使用多个患者队列评估关键基因MFAP2的预后价 值,分析其效能和临床病理指标的相关性。使用多个在线数据库数据及算法分析MFAP2与肿瘤免疫微环境的关联,免疫表型评分 (IPS)联合免疫治疗患者队列分析MFAP2在预测免疫治疗响应性中的价值。采用多数据集验证 MFAP2在胃癌及癌旁组织中 的表达差异。结果:蓝色模块与胃癌患者的生存结局相关性最高(R=0.17,P<0.001);进一步与预后相关基因取交集,共筛选到20个 关键基因。关键基因MFAP2的高表达提示胃癌的不良预后和病理进展(HR>1,P<0.05)。MFAP2与肿瘤相关成纤维细胞密切相关, 高表达MFAP2的胃癌患者对免疫治疗更不敏感。多数据集验证结果显示,MFAP2 mRNA在胃癌组织中高表达(P<0.05或P<0.01)。 结论:MFAP2的高表达是胃癌预后不良和免疫治疗响应不佳的提示因子,有望作为胃癌的新型治疗靶点和预后标志物。
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[Abstract]
Objective: To screen the key genes affecting the prognosis and treatment of gastric cancer (GC) patients and to analyze the value of the key gene microfibrillar-associated protein 2 (MFAP2) in suggesting the prognosis and the sensitivity of immunotherapy of GC patients. Methods: The expression profile data and clinical information of gastric cancer and paracancerous tissues were downloaded from the TCGA database. Genes significantly associated with the prognosis of gastric cancer were screened by weighted gene co-expression network analysis (WGCNA) and univariate Cox regression analysis. Multiple patient cohorts were used to assess the prognostic value of the key gene MFAP2 and analyze its efficacy and clinicopathological correlation. Multiple online databases and algorithms were used to analyze the correlation between MFAP2 and the tumor immune microenvironment. Immunophenotyping score (IPS) combined with immunotherapy patient cohort was used to analyze the value of MFAP2 in predicting the responsiveness of immunotherapy. Differential expression of MFAP2 in gastric cancer and adjacent tissues was verified with multiple datasets. Results: The blue module showed the highest correlation with survival outcomes of GC patients (R=0.17, PHR>1, PPPConclusion: High expression of MFAP2 is a predictive factor for poor prognosis and response to immunotherapy in GC patients. MFAP2 is expected to serve as a novel therapeutic target and prognostic indicator for gastric cancer.
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