基于生物信息学分析胃肠上皮化生关键基因及靶向中药

Bioinformatics-Based Analysis of Key Genes of Gastrointestinal Metaplasia and Targeting Traditional Chinese Medicines

目的:基于生物信息学方法分析胃肠上皮化生(intestinal metaplasia,IM)的关键基因、机制通路,并预测潜在靶向中药。方法:从GEO数据库获取GSE78523、GSE60427数据集,利用GEO2及R软件筛选IM差异表达基因并对其进行富集分析,通过STRING数据库和Cytoscape软件构建蛋白互作网络(protein-protein interaction,PPI),筛选关键基因,利用Kaplan-Meier Plotter数据库、GEPIA数据库及HPA数据库对关键基因进行生存分析及表达验证,在Coremine Medical数据库预测筛选潜在中药。结果:筛选出285个差异表达基因。基因本体功能富集分析显示,差异基因主要参与消化吸收、肠道脂质的调节与吸收等生物过程。京都基因和基因组百科全书通路富集分析主要涉及营养物质的消化和吸收、糖酵解/糖异生、胆汁分泌、胆固醇代谢等。获取的7个关键基因是APOB、FABP1、APOA1、APOA4、NR1H4、PCK1、ALDOB。筛选得到的潜在中药可分为健脾益气和胃、祛瘀通络、解毒祛邪三大类,符合胃IM健脾通络解毒的治则。结论:本研究筛选出7个与IM密切相关的核心基因,挖掘出可能用于胃癌前病变靶向治疗的中药。

Objective:To analyze the key genes and mechanistic pathways of Gastrointestinal metaplasia(IM)based on bioinformatics methods,and to predict potential targeted traditional Chinese medicines.Methods:The GSE78523 and GSE60427 datasets were obtained from the GEO database,the differentially expressed IM genes were screened and enriched by GEO2 and R software,the protein-protein interacton(PPI)network was constructed by STRING database and Cytoscape software,and the key genes were screened.The GEPIA database and HPA database were used for survival analysis and expression verification of key genes,and potential traditional Chinese medicines were predicted and screened in the Coremine Medical database.Results:A total of 285 differentially expressed genes were screened.Gene ontology function enrichment analysis showed that differential genes were mainly involved in biological processes such as digestion and absorption,regulation,and absorption of intestinal lipids.Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis mainly involves nutrient digestion and absorption,glycolysis/gluconeogenesis,bile secretion,cholesterol metabolism,etc.The 7 key genes obtained were APOB,FABP1,APOA1,APOA4,NR1H4,PCK1,and ALDOB.The potential Chinese medicines screened can be divided into three categories:strengthening the Spleen and invigorating Qi to harmonize the Stomach Qi,dispelling stasis to dredge the meridians as well as detoxifying and dispelling the evil factors,which are in line with the treatment principles of stomach IM to strengthen the Spleen and detoxify.Conclusion:In this research,7 core genes closely related to IM were screened,and traditional Chinese medicines that may be used for targeting therapy of gastric precancerous lesions were explored.