基于药物重定位策略挖掘肺腺癌治疗药物

Mining Lung Adenocarcinoma Therapeutic Drugs Based on Drug Repurposing Strategy

目的利用基因表达综合数据库(GEO)中肺腺癌患者癌和癌旁组织的全基因组表达数据,借助关联性图谱(CMAP)和生物信息学的方法探讨潜在的具有肺腺癌治疗作用的小分子药物。方法通过GEO数据库中的3个肺腺癌相关数据集(GSE10072、GSE87340、GSE40419),获得肺腺癌差异表达基因,之后借助CMAP数据库寻找肺腺癌的潜在治疗药物,并阐述可能的分子机制。结果利用肺腺癌的差异表达基因和CMAP数据库,筛选出洛贝林、苄普地尔、氯丙嗪、荜茇酰胺、碘化丙啶、奎尼卡因等共10种候选药物。上述药物对肺腺癌患者基因表达谱具有显著的负向调节作用,提示可能具有治疗肺腺癌的潜能。既往研究证实这些药物对肺腺癌有一定的治疗作用,验证了该药物筛选方法的可靠性。结论利用肺腺癌患者肺组织全基因组表达谱和CMAP数据库能够快速筛选出具有治疗潜能的药物,未来可对候选药物进行下一步体外、体内和临床试验以证实其治疗的安全性和有效性。

Objective Based on the whole genome expression data of lung adenocarcinoma patients and adjacent tissues in the Gene Expression Omnibus(GEO),the potential small molecule drugs for the treatment of lung adenocarcinoma are explored by means of Connectivity Map(CMAP)and bioinformatics.Methods The lung adenocarcinoma differentially expressed genes were obtained from three lung adenocarcinoma-related data sets in the GEO database(GSE10072,GSE87340,and GSE40419).The CMAP database was then used to find potential therapeutic drugs for lung adenocarcinoma and to explain possible molecular mechanisms.Results Using the differentially expressed genes of lung adenocarcinoma and the CMAP database,10 candidate drugs were screened out:lobelin,bepridil,chlorpromazine,propidium iodide,quinisocaine,etc.The above drugs had significant negative regulation effect on gene expression profiles of patients with lung adenocarcinoma,suggesting that they may have potential for treating lung adenocarcinoma.Previous studies had confirmed that these drugs had a certain therapeutic effect on lung adenocarcinoma,verifying the reliability of the drug screening method.Conclusion By analyzing the genome-wide expression profile of lung tissue of patients with lung adenocarcinoma and CMAP database,it is possible to quickly screen for drugs with potential to treat lung adenocarcinoma.In the future,candidate drugs can be tested in vitro,in vivo,and clinical trial to confirm the safety and effectiveness.