胃癌GEO芯片结合TCGA数据差异基因筛选、功能及通路研究

Screening and integrative analysis of GEO chips and TCGA data for differentially expressed genes in gastric cancer

目的筛选影响胃癌发生发展过程的相关基因及其通路,以探讨其发病机制。方法从基因表达数据库(GEO)中筛选数据集,利用GEO2R分析胃癌组织和正常组织中显著差异表达基因。使用Bio venn获得两数据集共有差异基因,将胃癌两GEO芯片共有差异表达基因数据与癌症基因组图谱(TCGA)数据库中筛选出的差异表达基因进行交集,并对其进行功能注释、KEGG富集、筛选核心互作基因,Kaplan-Meier plotter分析核心互作基因总体生存率。结果从GSE55696和GSE79973芯片中筛选出27个共有差异基因,与TCGA-STAD中有交集的差异表达基因有17个。涉及亨利恒等循环、葡萄糖的跨膜转运、胰岛素分泌的负调节和胆固醇生物合成等生物过程。主要存在于细胞外空隙、分泌颗粒内腔中,富集在金属羧肽酶活性功能方面。涉及PPAR信号通路、炎症介质对TRP通道的调节等39个通路,3个基因富集PPAR信号通路,7个基因互作关系较强,4个高表达基因生存曲线明显预后较差。结论核心基因SLC2A2、HMGCS2、APOA1、KNG1和PPAR信号通路可能是胃癌发生发展过程中的关键因素。

Objective To screen the core genes and related pathways in the pathogenesis of gastric cancer(GC)and the molecular mechanisms underlying GC pathogenesis.Methods Datasets were screened from the Gene Expression Omnibus(GEO)database.GEO2R was selected to analyze significantly differentially expressed genes(DEGs)in GC and normal tissues.Bio venn analysis revealed common DEGs in multiple datasets.Functional annotation,Kyoto Encyclopedia of Genes and Genomes enrichment,and selection of core interaction genes were performed.Kaplan-Meier plots were constructed to analyze the association of the core interaction genes with overall survival rate.Downloaded pathological data of The Cancer Genome Atlas Stomach Adenocarcinoma(TCGA-STAD)were used to screen DEGs.These genes were compared with the DEGs identified in the GEO GC microarray data.Results Twenty-seven common DEGs were screened in the GSE55696 and GSE79973 microchips.Of these,17 were also present in TCGA-STAD.These genes were involved in various biological processes,including Henry isocirculation,glucose transmembrane transport,and negative regulation of insulin secretion and cholesterol biosynthesis.The locales were mainly the extracellular void and secretory granule cavity and were functionally concentrated in metal carboxypeptidase activity.The 39 enriched pathways included the peroxisome proliferator-activated receptor(PPAR)signaling pathway and regulation of the transient receptor potential channel by inflammatory mediators.Three genes were enriched in the PPAR signaling pathway.Seven genes showed strong interactions with each other.The overall survival curves revealed an association between poor prognosis and the high expression of four genes.Conclusion SLC2A2,HMGCS2,APOA1,KNG1,and PPAR signaling pathways may be key factors associated with the development of GC.