基于开放数据的卵巢癌细胞铂类耐药机制分析和治疗药物选择研究  

Analysis of platinum resistance mechanism cells and selection of therapeutic drugs in ovarian cancer cells based on open data

作　　者：程琛[1] 具晟 戴建荣[1] 侯顺玉[1] CHENG Chen;JU Sheng;DAI Jianrong;HOU Shunyu(Department of Obstetrics and Gynecology,Suzhou Municipal Hospital,Suzhou,Jiangsu 215000,China;Suzhou University,Suzhou,Jiangsu 215000,China)

机构地区：[1]苏州市立医院本部妇产科,江苏苏州215000 [2]苏州大学,江苏苏州215000

出　　处：《现代医药卫生》2020年第24期3928-3935,共8页Journal of Modern Medicine & Health

基　　金：江苏省苏州市临床专家团队引进项目(SZJTD201707);江苏省苏州市立医院妇科临床试验机构能力提升项目(SLT201955);苏州妇产疾病临床医学中心项目(Szzx201505)。

摘　　要：目的探索卵巢癌细胞系耐药基因表达改变及其生物学机制,为卵巢癌细胞系铂类耐药成因及治疗提供生物信息学依据。方法从基因表达数据库(GEO)下载A2780耐铂类化疗和原始细胞株相关基因芯片数据集并分组,应用R软件筛选差异表达基因,使用clusterProfiler R包对差异基因进行基因本体论(GO)、京都基因与基因组百科全书(KEGG)富集分析和可视化,找出相关高度表达的基因通路。通过STRING数据库及Cytoscape软件构建蛋白互作网络,分析网络的hub基因。通过Cytoscape软件构建蛋白互作网络并分析生物过程。利用CMap网站,通过差异基因在细胞株内导致的药物反应区别,识别与耐药相关的药物。结果卵巢癌铂类耐药的形成在基因表达层面的关键变化基因数量较少,不同研究芯片同样高表达的基因仅有32个,低表达的基因仅有126个,细胞外基质信号通路和MAPK信号通路相关基因表达升高,外泌体分泌相关蛋白增加,胆固醇储存的正向调控过程增强,生长板软骨细胞分化,单核细胞分化等生物学过程增强,说明卵巢癌细胞耐铂类机制可以沿着上述2个机制探索。而Cycloheximide、Emetine、Cephaeline、Homoharringtonin、Verrucarin-A、Puromycin等6种药物可以在铂类耐药的生物学研究中有所侧重。结论本研究对人卵巢癌细胞铂类耐药成因及治疗进行了探索及分析,对人卵巢癌细胞铂类耐药的进一步研究提供了生物信息学理论依据。Objective To explore the changes in the expression of drug resistance genes in ovarian cancer cell lines and their biological mechanisms,and provide bioinformatics evidence for the cause and treatment of platinum resistance in ovarian cancer cell lines.Methods The A2780 platinum-resistant chemotherapy and original cell line related gene chip data set was downloaded from the Gene Expression Database(GEO)and grouped.R software was used to screen differentially expressed genes.The cluster Profiler R package was used to perform gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and visualization of differential genes to find out related highly expressed gene pathways.A protein interaction network was constructed through STRING database and Cytoscape software to analyze the hub gene of the network.Cytoscape software was used to construct a protein interaction network and analyze biological processes.The CMap website was used to identify drugs related to drug resistance through differentiation of drug reactions caused by differential genes in cell lines.Results The results of multi-chipset analysis showed that the formation of platinum resistance in ovarian cancer had a small number of key changes in gene expression.There were only 32 genes with the same high expression in different research chips,and only 126 genes with low expression.The expression of genes related to the extracellular matrix signaling pathway and MAPK signaling pathway increased.The secretion of proteins related to exosomes increased.The positive regulation of cholesterol storage was enhanced.The biological processes of growth plate chondrocyte differentiation and monocyte differentiation were enhanced,indicating that the platinum resistance mechanism of ovarian cancer cells could be explored along the above two mechanisms.Six drugs such as Cycloheximide,Emetine,Cephaeline,Homoharringtonine,Verrucarin-A,Puromycin could be focused on the biological research of platinum resistance.Conclusion This study explored and a

关 键 词：卵巢癌 耐药 差异表达基因 生物信息学 A2780细胞株 

分 类 号：R737.31[医药卫生—肿瘤]