基于生物信息学分析在胃癌发生发展及预后中的关键基因

Key genes influencing the development and progression of gastric cancer:A bioinformatics analysis

目的探讨基于肿瘤研究公共数据库TCGA和GTEx分析在胃癌中异常表达且与预后相关的基因。方法使用GEPIA生物信息学分析平台,对肿瘤研究公共数据库TCGA及基因型-组织表达数据库GTEx中胃癌及正常黏膜组织的关键差异mRNA进行分析,使用FUNRICH软件进行基因本体富集分析和通路分析,并筛选胃癌中异常表达并与预后相关的基因。结果共筛选到4644个差异基因,包括3746个上调基因,898个下调基因。上调表达前十位基因包括CEACAM5、CEACAM6、RNU11、CLDN3、CST1、OLFM4、REG4、MUC3A、MUC13和CLDN4,下调表达前十位基因包括GKN2、ATP4A、ATP4B、PGC、GIF、GKN1、LIPF、PGA5、PGA4和PGA3。与胃癌预后总生存时间最相关的100个基因中COL4A5、NT5E、ABCA8、MAGED4B、FABP4、CLRN3、ZNF662、PLCXD3、PDK4、NRP1、RAI14、SLC52A3、DPP3及SERPINE1等14个基因显著差异表达。其中SERPINE1、NT5E、NRP1和RAI14在胃癌中高表达,且生存分析提示,高表达与患者不良预后相关。结论SERPINE1、NT5E、NRP1和RAI14在胃癌中高表达且与预后不良密切相关,具有成为胃癌诊断的生物标记物或治疗靶点的潜力。

Objective To analyze genes which were abnormally expressed and influenced the prognosis of gastric cancer using public data bases of The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx).Methods Using GEPIA the bioinformatics analysis platform,primary differences in mRNA expression profile were analyzed in stomach cancer as well as in normal mucosa in TCGA a public database for cancer research and GTEx a genotype-tissue expression database.FUNRICH software was used to performed gene ontology enrichment analysis and pathway analysis.The abnormally expressed genes and genes influencing the prognosis of gastric cancer were screened out.Results A total of 4644 genes with differential expression were screened out including 3746 over-expressed genes and 898 down-expressed genes.The top 10 up-expressed genes included CEACAM5,CEACAM6,RNU11,CLDN3,CST1,OLFM4,REG4,MUC3 A,MUC13 and CLDN4 and the top 10 down-expressed genes included GKN2,ATP4 A,ATP4 B,PGC,GIF,GKN1,LIPF,PGA5,PGA4 and PGA3.Among the 100 genes which were mostly associated with survival,14 genes including COL4 A5,NT5 E,ABCA8,MAGED4 B,FABP4,CLRN3,ZNF662,PLCXD3,PDK4,NRP1,RAI14,SLC52 A3,DPP3 and SERPINE1 were significantly differentially expressed.Among them,NT5 E,SERPINE1,NRP1 and RAI14 genes were highly expressed in gastric cancer,and survival analysis suggested that the high expression of these genes was associated with poor prognosis.Conclusion SERPINE1,NT5 E,RAI14 and NRP1 were highly expressed in gastric cancer and associated with poor prognosis.They had the potential to become biomarker or therapeutic targets for gastric cancer.