胃腺癌相关关键基因的筛选及其调控通路研究

Identification and regulatory pathways analysis of hub genes in gastric adenocarcinoma

目的筛选胃腺癌(Gastric adenocarcinoma,GAC)差异表达的关键基因并进行验证,分析其调控通路。方法自美国国立生物技术信息中心基因表达数据库(Gene expression omnibus,GEO)下载GAC基因芯片数据集GSE118916。应用R语言Limma程序包筛选GAC与癌旁对照组织差异表达基因(Differentially expressed genes,DEGs)。应用R语言ClusterProfiler程序包对GAC的DEGs进行京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路分析。通过DAVID(Database for Annotation,Visualization and Integrated Discovery)数据库对GAC的DEGs进行基因本体(GO)功能富集分析。使用STRING(Search Tool for the Retrieval of Interacting Genes)和Cytoscape构建蛋白质间相互作用网络(PPI),筛选其核心模块和关键基因。使用UALCAN数据库分析关键基因与GAC患者预后的关系。GEPIA数据库分析预后关键基因与GAC患者TNM的相关性。采用单基因GSEA分析关键基因调控的通路。结果GAC癌组织和癌旁组织存在704个DEGs,其中上调基因422个,下调基因282个。GO功能富集结果显示,DEGs主要富集在细胞外基质组织、细胞粘附、炎症反应、胶原蛋白分解代谢等功能通路;KEGG通路分析显示,DEGs主要影响ECM-受体相互作用、黏着斑、补体通路等多条通路。在PPI网络筛选的关键基因中,C3、GNB4和COL1A2影响GAC患者预后和GAC进展。单基因GSEA结果显示,C3、GNB4和COL1A2可能通过黏着斑、癌症通路、干细胞Wnt信号、转化生长因子-β信号途径影响GAC患者的预后。结论C3、GNB4和COL1A2是影响GAC进展和预后的关键基因,其调控通路可能与黏着斑、癌症通路相关。

Objective This study aims to screen out the key prognostic genes,which were differentially expressed in gastric adenocarcinoma.Methods GSE118916 was downloaded from Gene expression omnibus database(GEO).Differentially expressed genes(DEGs)were identified by Limma package in R software.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis was performed for these DEGs using the ClusterProfiler package.Gene Ontology(GO)enrichment analysis was conducted by using DAVID database.The Search Tool for the Retrieval of Interacting Genes(STRING)database and Cytoscape was used to construct the protein-protein interaction network(PPI).MCODE and cytoHubba in Cytoscape were used to identify the core modules and the hub genes in PPI network.UALCAN database was used to analyze the relationship between hub genes and prognosis of patients with gastric adenocarcinoma.GEPIA database was used to analyze the association of expression of hub genes with the TNM stage.Gene set variation was used to analyze the hub genes related regulatory pathways.Results There were 704 differentially expressed genes,which including 422 up-regulated genes and 282 down-regulated genes,were screened out between gastric adenocarcinoma cancer tissue and adjacent normal tissues.Go enrichment analysis showed that the most DEGs were significantly enriched in extracellular matrix organization,cell adhesion,inflammation response and collagen catabolic process.KEGG pathway enrichment analysis suggested that the most DEGs were significantly participated in the ECM-receptor interaction,focal adhesion and complement and coagulation cascades.Among the hub genes identified by PPI network,C3,GNB4 and COL1A2 were significantly predicted to affect the prognosis and TNM stage of gastric adenocarcinoma.Single-gene GSEA showed that C3,GNB4 and COL1A2 might affect the prognosis of patients with gastric adenocarcinoma through adhesion plaque,cancer pathway and stem cell Wnt signaling pathway.Conclusion C3,GNB4 and COL1A2 may act as the hub genes related to the prognosis of patients with gastric adenocarcinoma and serve as the potential therapeutic targets of gastric adenocarcinoma.