基于生物信息学技术筛选结直肠癌的差异基因和中药预测研究

Screening of differentially expressed genes for colorectal cancer and prediction of potential traditional Chinese medicine:based on bioinformatics

通过生物信息学技术筛选并分析结直肠癌(colorectal cancer,CRC)与正常组织的差异基因,预测可用于诊断和治疗CRC的生物标志物及中药。从基因表达数据库(Gene Expression Omnibus,GEO)获取GSE21815、GSE106582、GSE41657基因芯片,应用GEO2R工具获取差异表达基因(differentially expressed genes,DEGs);应用DAVID数据库对DEGs进行基因本体论(Gene Ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析;通过STRING数据库构建蛋白-蛋白互作网络,应用MCODE、CytoHubba插件筛选网络中显著模块及关键基因;分别应用UCSC、cBioPortal、Oncomine在线数据库对关键基因进行分层聚类、生存分析、Oncomine分析和临床资料相关性分析;应用Coremine Medical数据库预测作用于关键基因的中药。共筛选出284个DEGs,其中146个上调基因,138个下调基因。上调基因显著富集在细胞周期、NLRs通路、TNF信号通路等途径;下调基因显著富集在矿物质吸收、氮代谢、碳酸氢盐在近端小管重吸收等通路。15个关键基因为CDK1、CDC20、AURKA、MELK、TOP2A、PTTG1、BUB1、CDCA5、CDC45、TPX2、NEK2、CEP55、CENPN、TRIP13、GINS2,其中CDK1和CDC20被视为核心基因。CDK1和CDC20的高表达有着较差的生存预后,并且它们在多种癌症中显著表达,尤其是乳腺癌、肺癌、CRC;CDK1和CDC20的表达与性别、肿瘤类型、TNM分期、KRAS基因突变具有相关性。预测出治疗CRC的潜在中药代表药物有黄芩、半枝莲、紫草等。CDK1和CDC20的显著表达有助于区分肿瘤组织和正常组织,并与生存预后有关,有望成为诊断和治疗CRC的生物标志物,该研究为将来新型药物的开发提供参考方向。

This study screened and analyzed the differentially expressed genes(DEGs)between colorectal cancer(CRC)tissues and normal tissues with bioinformatics techniques to predict biomarkers and Chinese medicinals for the diagnosis and treatment of CRC.The microarray data sets GSE21815,GSE106582,and GSE41657 were downloaded from the Gene Expression Omnibus(GEO),and the DEGs were screened by GEO2 R,followed by the Gene Ontology(GO)tern enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of the DEGs based on DAVID.The protein-protein interaction network was constructed by STRING,and MCODE and Cytohubba plug-ins were used to screen the significant modules and hub genes in the network.UCSC,cBioPortal,and Oncomine were employed for hierarchical clustering,survival analysis,Oncomine analysis,and correlation analysis of clinical data.Coremine Medical was applied to predict the Chinese medicinals acting on hub genes.A total of 284 DEGs were screened out,with 146 up-regulated and 138 down-regulated.The up-regulated genes were mainly involved in cell cycle,NLRs pathway,and TNF signaling pathway,and the down-regulated genes were related to mineral absorption,nitrogen metabolism,and bicarbonate reabsorption in proximal tubules.The 15 hub genes were CDK1,CDC20,AURKA,MELK,TOP2 A,PTTG1,BUB1,CDCA5,CDC45,TPX2,NEK2,CEP55,CENPN,TRIP13,and GINS2,among which CDK1 and CDC20 were regarded as core genes.The high expression of CDK1 and CDC20 suggested poor prognosis,and they significantly expressed in many cancers,especially breast cancer,lung cancer,and CRC.The expression of CDK1 and CDC20 was correlated with gender,tumor type,TNM stage,and KRAS gene mutation.The potential effective medicinals against CRC were Scutellariae Radix,Scutellariae Barbatae Herba,Arnebiae Radix,etc.The significant expression of CDK1 and CDC20 can help distinguish tumor tissues from normal tissues,and is related to survival prognosis.Thus,the two can be used as biomarkers for the diagnosis and treatment of CRC.This study provides a reference for related drug development.