胃癌枢纽基因的筛选和预后分析

Identifi cation and prognostic analysis of hub genes in gastric cancer

目的:运用生物信息学方法探讨胃癌的预测指标和治疗靶点,并分析其与预后的关系。方法:从基因表达综合(GEO)数据库下载3个微阵列数据集(GSE13911、GSE33651、GSE79973),运用GEO2R筛选出胃癌样本与正常组织样本间的差异表达基因,通过基因本体论(GO)富集分析和京都基因与基因组百科全书(KEGG)分析对差异基因进行功能和通路注释,同时使用STRING和Cytoscape构建蛋白互作网络(PPI),筛选出枢纽基因,结合Kaplan-Meier plotter数据库对筛选出的枢纽基因进行预后分析。结果:共筛选出135个差异表达基因,其中68个上调,67个下调。GO分析结果表明差异表达基因主要参与信号转导、钙离子结合、细胞外外泌体等生物学过程。KEGG分析显示差异基因主要富集的通路包括PI3K/Akt信号通路、ECM受体相互作用、黏着斑。经PPI分析筛选得出COL1A1、COL1A2、COL4A1、FN1、THBS1、CD44、COL2A1、COL4A2、CXCL8、COL5A1为枢纽基因,生存分析显示除THBS1的上调,其余基因的差异表达均影响胃癌患者的总体生存率。结论:所筛选的枢纽基因的异常表达可能参与胃癌的发生发展过程,与胃癌患者的预后密切相关,可以作为潜在的预测指标和治疗靶点为胃癌的进一步研究提供依据。

Objective:To investigate the predictive indicators and therapeutic targets of gastric cancer using bioinformatics approach and analyze the relations of them with prognosis.Methods:Three microarray datasets(GSE13911,GSE33651,GSE79973)were downloaded from Gene Expression Omnibus(GEO)database.The differentially expressed genes between gastric cancer samples and normal tissue samples were screened using GEO2 R tools.The functional and pathway annotations of thediff erentially expressed genes were performed by Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses,Meanwhile,the protein-protein interaction network(PPI)was constructed using STRING and Cytoscape to pick up the hub genes,and the relations of the hub genes with prognosis were analyzed using the Kaplan-Meier plott er database.Results:A total of 135 diff erentially expressed genes were screened,of which 68 were up-regulated and 67 were down-regulated.GO analysis showed that the diff erentially expressed genes were mainly enriched in biological processes such as signal transduction,calcium ion binding and extracellular exosomes.KEGG analysis revealed that the major enriched pathways of the differentially expressed genes included PI3 K/Akt signaling pathways,ECM receptor interactions and focal adhesions.PPI analysis showed that COL1 A1,COL1 A2,COL4 A1,FN1,THBS1,CD44,COL2 A1,COL4 A2,CXCL8,COL5 A1 were the hub genes.Survival analysis showed that except the up-regulation of THBS1,the abnormal expressions of other hub genes were signifi cantly associated with the overall survival of the gastric cancer patients.Conclusion:The abnormal expressions of the screened hub genes may be involved in the development and progression of gastric cancer,and could be closely related to the prognosis of gastric cancer patients.Th ese genes may serve as potential predictors and therapeutic targets for further research of gastric cancer.