基于药物重定位策略挖掘放射性肺纤维化潜在预防药物

Potential Preventive Drugs for Radiation-Induced Pulmonary Fibrosis Based on Drug Repositioning Strategies

目的通过药物重定位来确定放射性肺纤维化的候选预防药物。方法从基因表达综合数据库下载基因芯片GSE2250和GSE41789,处理后获得差异表达基因。利用LINCS数据库识别出可能逆转差异表达基因的已上市药物。最后利用OpenFDA数据平台确定这些药物的安全性,得到候选预防性药物。结果分析数据集GSE2250和GSE41789的基因表达情况,得到42个共同差异表达基因。利用L1000CDS2分析工具筛选出可能逆转放射性肺纤维化的药物,包括曲美替尼、扑米酮、司美替尼、米托蒽醌和奎纳克林。使用OpenFDA数据平台得知米托蒽醌可能会增加放射性肺纤维化不良事件发生风险,遂将其排除,因此将曲美替尼、扑米酮、司美替尼和奎纳克林确定为候选预防药物。结论曲美替尼、扑米酮、司美替尼和奎纳克林为抗放射性肺纤维化的潜在预防药物。

Objective To identify candidate preventive drugs for radiation-induced pulmonary fibrosis using drug repositioning.Methods Microarray GSE2250 and GSE41789 were downloaded from the GEO database and processed to obtain differently expressed genes(DEGs).The LINCS database was searched to identify marketed drugs that could reverse the expression of DEGs.Finally,the OpenFDA data platform was leveraged to assess the safety of these drugs to find out which were safe and valid candidate preventive drugs.Results The gene expressions of GSE2250 and GSE41789 in the dataset were analyzed,resulting in 42 common DEGs.L1000CDS2 analysis screened out drugs that might reverse radiation-induced pulmonary fibrosis,including Trametinib,Primidone,Selumetinib,Mitoxantrone and Quinacrine.In the OpenFDA data platform,it was concluded that Mitoxantrone was likely to increase the risk of adverse events for radiation-induced pulmonary fibrosis,so it was removed from the list,leaving Trametinib,Primidone,Selumetinib and Quinacrine as candidate preventive drugs.Conclusion Trametinib,primidone,selumetinib and quinacrine can potentially work as anti-radiation-induced pulmonary fibrosis drugs.