背景:胃癌是全球最常见的恶性肿瘤之一。尽管近年来对该疾病的诊断和治疗已有实质性改善,但由于局部复发和远处转移,胃癌的五年生存率仍然较低。对胃癌分子发病机理及相关预后标志物的深入研究将有助于改善胃癌患者的生活质量和预后。这项研究的目的是鉴定和验证具有胃癌预后价值的SNP突变基因并探索其在胃癌中的应用价值。方法:从癌症基因组图谱(TCGA)数据库中获得胃癌患者的SNP相关数据,并使用DAVID软件分析突变基因的功能和下游通路。使用STRING数据库构建蛋白质–蛋白质相互作用(PPI)网络,并通过Cytoscape软件可视化。分子复合物检测(MCODE)用以筛选PPI网络以提取重要的突变基因,使用cytoHubba鉴定了10个中枢基因,并通过UALCAN和Kaplan-Meier Plotter网站确定了中枢基因的表达水平和预后。最后,定量PCR和蛋白质印迹实验被用来验证中枢基因在胃癌细胞中的表达。结果:从数据库中鉴定出超过25个样本中的945个SNP突变基因。PPI网络具有360个节点和1616个边缘。最后,cytoHubba鉴定了六个关键基因(TP53,HRAS,BRCA1,PIK3CA,AKT1和SMARCA4),它们的表达水平与胃癌患者的生存率密切相关。结论:我们的结果表明,SNP突变相关基因TP53,HRAS,BRCA1,PIK3CA,AKT1和SMARCA4可能是胃癌发展和预后的关键基因。本研究为进一步探索胃癌的分子发病机制和评估患者预后提供了重要的生物信息学基础和相关的理论基础。
Gastric cancer is one of the most common malignancies worldwide. An in-depth study of the molecular pathogenesis of gastric cancer and related prognostic markers will help improve the quality of life and prognosis of patients with this disease. The purpose of this study was to identify and verify key SNPs in genes with prognostic value for gastric cancer. SNP-related data from gastric cancer patients were obtained from The Cancer Genome Atlas (TCGA) database, and the functions and pathways of the mutated genes were analyzed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) software. A protein-protein interaction (PPI) network was constructed using the STRING database and visualized by Cytoscape software, and molecular complex detection (MCODE) was used to screen the PPI network to extract important mutated genes. Ten hub genes were identified using cytoHubba, and the expression levels and the prognostic value of the central genes were determined by UALCAN and Kaplan-Meier Plotter. Finally, quantitative PCR was used to verify the expression of the hub genes in gastric cancer cells. From the database, 945 genes with mutations in more than 25 samples were identified. CytoHubba identified six key SNP-containing genes (TP53, HRAS, BRCA1, PIK3CA, AKT1, and SMARCA4), and their expression levels were closely related to the survival rate of gastric cancer patients. Our research provides an important bioinformatics foundation and related theoretical foundation for further exploring the molecular pathogenesis of gastric cancer and evaluating the prognosis of patients. Further investigations of SNP-containing genes in gastric cancer may contribute to therapeutic advances.
胃癌,单核苷酸多态性,生物标志物,预后,生物信息学分析, Gastric Cancer Single Nucleotide Polymorphisms Biomarkers Prognosis Bioinformatics Analysis摘要
Gastric cancer is one of the most common malignancies worldwide. An in-depth study of the molecular pathogenesis of gastric cancer and related prognostic markers will help improve the quality of life and prognosis of patients with this disease. The purpose of this study was to identify and verify key SNPs in genes with prognostic value for gastric cancer. SNP-related data from gastric cancer patients were obtained from The Cancer Genome Atlas (TCGA) database, and the functions and pathways of the mutated genes were analyzed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) software. A protein-protein interaction (PPI) network was constructed using the STRING database and visualized by Cytoscape software, and molecular complex detection (MCODE) was used to screen the PPI network to extract important mutated genes. Ten hub genes were identified using cytoHubba, and the expression levels and the prognostic value of the central genes were determined by UALCAN and Kaplan-Meier Plotter. Finally, quantitative PCR was used to verify the expression of the hub genes in gastric cancer cells. From the database, 945 genes with mutations in more than 25 samples were identified. CytoHubba identified six key SNP-containing genes (TP53, HRAS, BRCA1, PIK3CA, AKT1, and SMARCA4), and their expression levels were closely related to the survival rate of gastric cancer patients. Our research provides an important bioinformatics foundation and related theoretical foundation for further exploring the molecular pathogenesis of gastric cancer and evaluating the prognosis of patients. Further investigations of SNP-containing genes in gastric cancer may contribute to therapeutic advances.
Keywords:Gastric Cancer, Single Nucleotide Polymorphisms, Biomarkers, Prognosis, Bioinformatics Analysis
李 晖,吴 昊,马英骥,梁志威,王功竣,齐卫卫,邱文生. 基于生物信息学鉴定和分析SNP突变基因在胃癌中的预后和应用价值Identification and Validation of SNP-Containing Genes with Prognostic Value in Gastric Cancer via Integrated Bioinformatics Analysis[J]. 临床医学进展, 2020, 10(11): 2832-2847. https://doi.org/10.12677/ACM.2020.1011430
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