利用生物信息学技术探索人卵巢癌细胞株A2780对顺铂耐药基因的研究  

Exploration of Cisplatin Resistance Gene in Human Ovarian Cancer Cell Line A2780 by Using Bioinformatics Technology

作　　者：张丽[1] 董冰莹 袁小丽 陈小斌 ZHANG Li;DONG Bingying;YUAN Xiaoli(Department of Gynecology,3201 Hospital of Xi′an Jiaotong University Health Science Center,Hanzhong Shanxi 723000,China)

机构地区：[1]西安交通大学医学部附属三二○一医院妇科,陕西汉中723000 [2]浙江大学医学院附属妇产科医院妇科,浙江杭州310000

出　　处：《实用妇产科杂志》2023年第6期465-469,共5页Journal of Practical Obstetrics and Gynecology

摘　　要：目的:利用生物信息学技术探索人卵巢癌细胞株A2780对顺铂耐药基因的可能机制,为临床化疗提供有效的依据。方法:①通过GEO在线GEO2R工具从两组数据库(GSE15372和GSE33482)中,分别比较对顺铂耐药的A2780与对顺铂敏感的A2780中的基因表达差异,并筛选出高表达基因和低表达基因;使用维恩图确定两组数据库中耐药的高表达共同差异基因和低表达的共同差异基因。②利用GO分析和KEGG通路富集分析耐药基因的生物学功能。③利用蛋白质-蛋白质互作(PPI)网络及Cytoscape软件筛选出A2780对顺铂耐药核心靶基因。④利用Kaplan-Meier Plotter工具对Hub基因进行总生存期分析。结果:①两组数据集的高表达共同耐药基因共37个,低表达共同耐药基因共2个。②GO分析结果显示:生物学过程(BP)分析结果表明,耐药基因主要参与着细胞间信号传导、趋化作用等;细胞组成(CC)分析表明,耐药基因主要位于细胞外区域、细胞间隙、细胞表面;分子功能(MF)分析表明,耐药基因参与着趋化因子相结合等作用。KEGG通路富集分析显示,耐药基因主要在细胞因子与细胞因子受体相互作用的信号通路、趋化因子信号通路上发挥作用。③PPI网络及Hub基因筛选结果显示:CCR5、POSTN、LOX、DACT1、RTN1、CCR1、CXCL6、PITX2、SNCA、AREG是核心耐药基因。④Hub基因中POSTN、LOX、DACT1、RTN1、PITX2的高表达与卵巢癌的不良预后有关(P<0.05)。结论:人卵巢癌细胞株A2780中顺铂耐药基因的异常表达,在卵巢癌化疗耐药中发挥着重要的作用,需要进一步的体外实验研究来证实其在临床化疗耐药中的作用。Objective:This study used bioinformatics technology to explore the possible mechanism of cisplatin resistance genes in human ovarian cancer cell line A2780,providing an effective basis for clinical chemotherapy.Methods:①We compared the gene expression difference between cisplatin-resistant A2780 and cisplatin-sensitive A2780 from two sets of databases(GSE15372 and GSE33482)by GEO online GEO2R tool,and screened the up-regulated genes and down-regulated genes.The Venn diagram was used to determine the up-regulation of common differential genes and down-regulated common differential genes in the two sets of databases.②The biological functions of drug resistance genes were ananlyzed by GO analysis and KEGG pathway enrichment.③To screen A2780-resistant cisplatin-resistant core target genes we used the protein-protein interaction(PPI)network and Cytoscape software.④The Kaplan-Meier Plotter tool was used to analyze the overall survival of the Hub genes.Results:①The combined results of the two sets of data sets were as followed,37 drug resistance genes were Up-regulated;two drug resistance genes were down-regulated.②The results of GO analysis were showed as following:BP analysis indicated that drug-resistant genes were mainly involved in intercellular signal transduction,chemotaxis,etc.CC analysis showed that drug-resistant genes were mainly located in the extracellular region,intercellular space and cell surface.MF analysis showed that drug-resistant genes were involved in chemokine binding and other roles.The results of KEGG pathway analysis showed that drug resistance genes mainly functioned in the cytokine-cytokine receptor interaction signaling pathway and the chemokine signaling pathway.③PPI network and Hub gene screening results showed that CCR 5,POSTN,LOX,DACT 1,RTN 1,CCR 1,CXCL 6,PITX 2,SNCA and AREG were core drug resistance genes.④The high expression of POSTN,LOX,DACT 1,RTN 1,PITX 2 in Hub genes were related to the poor prognosis of ovarian cancer(P<0.05).Conclusions:The aberrant expression of

关 键 词：卵巢癌 细胞株A2780 顺铂 耐药基因 生物学信息技术 

分 类 号：R737.31[医药卫生—肿瘤]