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中华普通外科学文献(电子版) ›› 2022, Vol. 16 ›› Issue (01) : 20 -26. doi: 10.3877/cma.j.issn.1674-0793.2022.01.004

论著

通过生物信息学分析发现胃癌的靶点基因和生物学特性
丁相元1, 严思奇1, 柳俊杰2, 颜伟1,()   
  1. 1. 434023 荆州市第一人民医院肿瘤外科
    2. 434023 荆州市第一人民医院放射科
  • 收稿日期:2021-04-21 出版日期:2022-02-01
  • 通信作者: 颜伟

Identification of hub genes and biological characteristics of gastric cancer by multiple-microarray analysis

Xiangyuan Ding1, Siqi Yan1, Junjie Liu2, Wei Yan1,()   

  1. 1. Department of Oncology, the First People’ s Hospital of Jingzhou, Jingzhou 434023, China
    2. Department of Radiology, the First People’ s Hospital of Jingzhou, Jingzhou 434023, China
  • Received:2021-04-21 Published:2022-02-01
  • Corresponding author: Wei Yan
引用本文:

丁相元, 严思奇, 柳俊杰, 颜伟. 通过生物信息学分析发现胃癌的靶点基因和生物学特性[J/OL]. 中华普通外科学文献(电子版), 2022, 16(01): 20-26.

Xiangyuan Ding, Siqi Yan, Junjie Liu, Wei Yan. Identification of hub genes and biological characteristics of gastric cancer by multiple-microarray analysis[J/OL]. Chinese Archives of General Surgery(Electronic Edition), 2022, 16(01): 20-26.

目的

从公共数据库获取数据,筛选差异表达基因,旨在发现胃癌潜在的靶点基因并揭示其生物学特征。

方法

基因表达谱(GSE29272、GSE54129、GSE13911、GSE79973、GSE19826)从GEO数据库获得;差异表达基因通过GEO2R筛选出,韦恩图绘制出5个基因表达谱的交集,从而得出共同差异表达基因;使用DAVID数据库进行共同差异表达基因的KEGG通路分析和GO富集分析;共同差异表达基因通过STRING数据库获取其蛋白质-蛋白质互作(PPI)网络图并用Cytoscape软件进行可视化,同时通过Cytoscape软件中的插件CytoHubba筛选胃癌靶点基因;靶点基因在GEPIA数据库和UALCAN数据库中进一步验证其表达及生存分析;CMap数据库预测其潜在的靶向小分子化合物。

结果

韦恩图筛选出105个共同差异表达基因,其中包括57个下调基因和48个上调基因;经DAVID数据库中的KEGG通路分析和GO富集分析显示,这些上调基因主要与细胞外基质组织、细胞黏附、局灶性黏附、PI3K-Akt信号传导途径、细胞外基质-受体相互作用相关。通过Cytoscape软件筛选出8个靶点基因:BGN、SPARC、COL5A2、COL5A1、COL1A2、COL4A1、COL6A3和COL11A1;在GEPIA数据库和UALCAN数据库验证后,确认了这8个关键基因与胃癌发生发展有关。生存分析显示,COL4A1(P=0.029,HR=1.4)和COL5A2(P=0.009 5,HR=1.5)的高表达与生存能力降低有关。CMap数据库分析显示吡咯酰胺和芳香维甲酸最有可能逆转胃癌的状态。

结论

BGN、SPARC、COL5A2、COL5A1、COL1A2、COL4A1、COL6A3和COL11A1可能被用作改善胃癌诊断和免疫疗法生物标志物的潜在靶标,吡咯酰胺和芳香维甲酸最有可能成为治疗胃癌的小分子化合物,这些分析结果为胃癌的病因研究提供了新的方向,也为深入探究其发病机制提供了理论基础。

Objective

To investigate the potential target genes of gastric cancer and reveal their biological characteristics.

Methods

Gene expression profiles (GSE29272, GSE54129, GSE13911, GSE79973, GSE19826) were obtained from GEO database. Differentially expressed genes were screened out by GEO2R, and the Venn diagram plotted the intersection of five gene expression profiles to obtain common differentially expressed genes. DAVID database was used to analyze the KEGG pathway and GO enrichment analysis of the common differentially expressed genes. The protein-protein interaction (PPI) network diagram of the common differentially expressed genes were obtained through the STRING database and visualize it with Cytoscape software, and used the plug-in in Cytoscape software at the same time CytoHubba screened gastric cancer target genes. The target genes were further verified in the GEPIA database and UALCAN database for their expression and survival analysis. The CMap database predicted its potential targeted small molecule compounds.

Results

The Venn diagram screened 105 common differentially expressed genes, including 57 down-regulated genes and 48 up-regulated genes. The KEGG pathway analysis and GO enrichment analysis in the DAVID database showed that these up-regulated genes were mainly related to extracellular matrix tissues, cell adhesion, focal adhesion, PI3K-Akt signaling pathway, and "ECM-receptor interaction". Eight target genes were screened by Cytoscape software: BGN, SPARC, COL5A2, COL5A1, COL1A2, COL4A1, COL6A3 and COL11A1. After verification in the GEPIA database and UALCAN database, it was confirmed that these eight key genes were related to the occurrence and development of gastric cancer. Survival analysis showed that the high expression of COL4A1 (Log rank P=0.029, HR=1.4) and COL5A2 (Log rank P=0.009 5, HR=1.5) was related to the decrease of survival ability. Analysis of the CMap database showed that pyrrolamide and TTNPB were the most likely to reverse the state of gastric cancer.

Conclusions

BGN, SPARC, COL5A2, COL5A1, COL1A2, COL4A1, COL6A3 and COL11A1 genes may be used as potential targets for improving gastric cancer diagnosis and immunotherapy biomarkers. Pyrrolamide and TTNPB are most likely to be small molecule compounds for the treatment of gastric cancer. These analysis results provide a new direction for the study of the etiology of gastric cancer, and also provide a theoretical basis for in-depth exploration of its pathogenesis.

表1 来自不同基因表达数据集的胃癌微阵列数据集
图1 韦恩图筛选差异表达基因
图2 通过Cytoscape软件可视化PPI网络的结果
图3 GEPIA数据库中靶点基因的表达 A为GEPIA数据库中8个靶点基因的表达,B为通过UALCAN数据库对8个靶点基因进行验证
图4 使用cBioPortal探索胃癌靶点基因的基因组变化
图5 胃癌关键基因的生存分析
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