联合GEO和TCGA数据库筛选子宫内膜癌关键基因和靶向药物

Screening of Hub Genes and Targeted Drugs in Endometrial Carcinoma by Combining GEO with TCGA databases

目的利用生物信息学技术筛选子宫内膜癌(endometrial carcinoma,EC)的差异表达基因(differentially expressed genes,DEGs)及潜在的治疗药物,为诊断和治疗EC提供理论依据。方法筛选了高通量基因表达数据库(Gene Expression Omnibus,GEO)GSE17025和癌症基因组图谱(The Cancer Genome Atlas,TCGA)子宫内膜癌数据库的重叠差异表达基因,用R语言筛选DEGs,并进行GO和KEGG富集分析。使用String工具分析差异基因编码蛋白互作(protein-protein interaction,PPI)网络,通过Cytoscape软件进行可视化展示,获得最显著模块基因以及关键基因,并对关键基因做靶向药物预测。结果通过GEO和TCGA筛选出上调基因269个、下调基因132个。GO富集分析结果显示,DEGs主要富集于纺锤体、细胞器分裂、受体配体活性等;KEGG信号通路分析,DEGs主要富集于细胞因子-细胞因子受体相互作用、白细胞介素-17(interleukin-17,IL-17)、细胞周期等信号通路。PPI网络中CDCA2、AURKA、DLGAP5、BIRC5、KIF11、CENPE、NCAPH、CCNB1、CDCA5、NCAPG被筛选为关键基因。在毒性与基因比较数据库(Comparative Toxicogenomics Database,CTD)中筛选出阿霉素、舒尼替尼和丙戊酸作为可能的靶向药物。结论利用生物信息学方法筛选的关键基因可能在EC的发生、发展中具有重要作用,可作为相关候选药物筛选的理论依据。

Objective Bioinformatics method was used to screen differentially expressed genes(DEGs)and potential therapeutic drugs for endometrial carcinoma(EC),and to provide theoretical basis for diagnosis and treatment of EC.Methods The overlapping DEGs of GSE17025 on Gene Expression Omnibus(GEO)and EC database on The Cancer Genome Atlas(TCGA)were screened,which were next screened in the R language and analyzed by GO and KEGG enrichment analysis.The String tool was used to analyze the protein-protein interaction(PPI)Networks encoded by DEGs,and Cytoscape software was used for visual presentation,to obtain the most significant module genes and key genes,and predict targeted drugs for key genes.Results A total of 269 up-regulated and 132down-regulated DEGs were screened out through GEO and TCGA.The results of GO enrichment analysis showed that DEGs were mainly involved in spindle,organelle fission,receptor ligand activity,etc.The KEGG signaling pathway analysis showed that DEGs were mainly enriched in cytokine-cytokine receptor interaction,interleukin-17(IL-17)and cell cycle and other signaling pathway.CDCA2,AURKA,DLGAP5,BIRC5,KIF11,CENPE,NCAPH,CCNB1,CDCA5 and NCAPG in the PPI network were screened as the key genes.Doxorubicin,sunitinib and valproic acid were screened out from Comparative Toxicogenomics database(CTD)as possible target drugs.Conclusion The Key genes screened out by the bioinformatics method may play a important role in the occurrence and development of EC,which would be a theoretical basis for related candidate therapeutic drugs.