基于药物重定位策略预测治疗多发性骨髓瘤的候选化合物

Prediction of candidate compounds for treatment of multiple myeloma(MM)based on drug reposition strategy

采用药物重定位(Drug repositioning,DR)策略预测多发性骨髓瘤的候选化合物,为多发性骨髓瘤的治疗提供新的思路和方向。利用GEO数据库检索并筛选多发性骨髓瘤表达谱芯片数据,GEO2R软件提取差异表达基因(DEGs);DAVID和Panther数据库对差异表达基因进行富集和通路分析;利用STRING数据库构建蛋白-蛋白相互作用网络分析;将差异表达基因导入CMAP连接图,计算获得治疗MM的候选化合物,进一步对候选化合物进行查找和分析。结果显示:共获得差异表达基因53个,包括上调差异表达基因10个、下调差异表达基因43个;GO分析结果表明生物学过程涉及22个功能簇,分子功能涉及5个功能簇,细胞成分涉及5个功能簇;KEGG分析涉及10条通路;蛋白-蛋白相互作用网络分析显示VCAM1、CCR2、CCL3和CXCL12等4个基因为富集程度最高的核心差异表达基因;通过CMAP连接图计算得到排名前20的候选化合物,其中LY-294002和Tanespimycin可能对MM有潜在治疗作用,但还有待深入试验研究和临床验证。

The purpose of this article is to use drug repositioning(DR)strategies to predict candidate compounds for multiple myeloma,and to provide new ideas and directions for the treatment of multiple myeloma.The GEO database was used to retrieve and screen the multiple myeloma expression profile chip data,GEO2R software was used to extract differentially expressed genes(DEGs);DAVID and Panther databases were used to enrich and differentially analyze differentially expressed genes;and the STRING database was used to construct a protein-protein interaction network analysis;the differentially expressed genes were introduced into the CMAP connection map,and candidate compounds for MM were calculated and obtained,and the candidate compounds were further searched and analyzed.It was found that a total of 53 differentially expressed genes were obtained,including 10 differentially up-regulated genes and 43 differentially down-regulated genes;GO analysis showed that biological processes involved 22 functional clusters,molecular functions involved 5 functional clusters,and cellular components involved 5 functional clusters;KEGG analysis involved 10 pathways;analysis of protein-protein interaction network showed that VCAM1,CCR2,CCL3 and CXCL12 genes were the core enriched genes with the highest enrichment;the top 20 were calculated by CMAP connection map candidate compounds,of which LY-294002 and Tanespimycin might have potential therapeutic effects on MM,but further experimental research and clinical verification were needed.