胶质母细胞瘤耐药性基因筛选及治疗药物预测OA
Drug Resistance Gene Screening and Therapeutic Drug Prediction of Glioblastoma
目的 运用生物信息学技术筛选胶质母细胞替莫唑胺(GBM TMZ)耐药差异表达基因(DEGs),探寻关键耐药基因及发病机制,并预测相关作用中药.方法 在GBM、GEO2R和GPEIA等多种数据库基础上进行生物学功能及通路富集分析,构建蛋白互作网络筛选关键基因,检索关键基因在正常人、胶质瘤患者组织中mRNA表达及生存率的影响.利用COREMINE平台对关键耐药基因构建药物-活性成分-作用靶点网络,筛选相关中药活性成分.结果 共筛选出 293 个DEGs,涉及FN1、CD44、CTGF、FOS等关键靶点,其表达显著高于正常人,影响患者总生存率,是GBM有害预后因素,但不会影响无复发生存率.影响细胞粘附、神经系统发育、转化生长因子β受体信号传导和基因正向调节等生物学功能.经COREMINE预测发现,与FN1 关系密切的干预药物多归属肝经,性味多以清热类和补虚类为主.结论 筛选出 12 个与GBM TMZ耐药相关的关键基因,FN1在TMZ耐药发生发展中起重要作用,木香、青叶胆及蓖麻子的活性成分可能作为TMZ耐药治疗药物来源.
Objective To screen differentially expressed genes(DEGs)of temozolomide(TMZ)resistance in glioblastoma cells(GBM)by bioinformatics technology,explore the key drug resistance genes and pathogenesis,and predict the related traditional Chinese medicine.Methods Based on GBM,GEO2R,GPEIA and other databases,biological function and pathway enrichment analysis were carried out,and protein interaction network was constructed to screen key genes.The effects of key genes on mRNA expression and survival rate in normal human and glioma patients were searched.The COREMINE platform was further used to construct a drug-active ingredient-target network for key drug resistance genes,and the active ingredients of related Chinese medicines were screened.Results A total of 293 DEGs were screened,involving key targets such as FN1,CD44,CTGF,and FOS.The expression was significantly higher than that of normal people,affecting the overall survival rate of patients,and was a harmful prognostic factor for GBM,but it did not affect the recurrence-free survival rate.While it affected biological functions such as cell adhesion,nervous system development,transforming growth factor β receptor signal transduction and gene positive regulation.It was predicted by COREMINE that the intervention drugs closely related to FN1 were mostly attributed to the liver meridian,and the nature and flavor were mainly heat-clearing and deficiency-tonifying.Conclusion Twelve key genes related to TMZ resistance in GBM were screened out.FN1 plays an important role in the occurrence and development of TMZ resistance.The active components of Muxiang,Qingyedan and Bimazi may be used as the source of TMZ resistance drugs.
初晓玲;吴波;蓝晓红;易剑峰;李薛梅;陈旭青
东部战区总医院药剂科,江苏 南京 210002江西中医药大学中医基础理论分化发展研究中心,江西 南昌 330004
药学
胶质母细胞瘤替莫唑胺耐药基因生物信息学中药预测
GlioblastomaTemozolomideDrug resistance genesBioinformaticsTraditional Chinese medicine prediction
《医学信息》 2024 (019)
10-18 / 9
国家自然科学基金项目(编号:82060739)
评论