摘要
目的:通过分析非小细胞肺癌顺铂敏感株及耐药株的基因芯片表达数据,筛选差异基因及关键通路,构建蛋白相互作用网络,探讨关键集群功能。方法:从GEO数据库获得基因芯片表达数据,利用GEO2R工具筛选差异基因,通过STRING数据库和Cytoscape软件构建蛋白相互作用网络,经DAVID富集得到相关特征基因与信号通路信息。结果:通过芯片分析共获得481个差异表达基因,相比于敏感细胞株,顺铂获得性耐药细胞株中有418个上调基因和63个下调基因。差异基因功能主要富集在piRNA代谢、DNA甲基化修饰、细胞有丝分裂及细胞周期进程等信号通路。蛋白复合物预测得到主要功能集群6个,分别与细胞趋化性、细胞角化性、piRNA代谢过程、细胞因子受体相互作用、细胞因子分泌调节及染色质沉默相关生物进程相关。结论:本研究利用生物信息学方法,发现顺铂耐药细胞株特征基因及信号通路,其中SAA1、KRT5、TDRD9、BCL2A1、CSF1R和HIST1H1A等显著上调基因及其功能集团可能是非小细胞肺癌顺铂耐药的潜在分子机制,为临床精准治疗提供新的理论依据。
Objective: To screen differentially expressed genes(DEGs) and key pathways by analyzing the gene chip expression data of cisplatin sensitive and resistant strains of non-small cell lung cancer(NSCLC), and to explore the key cluster functions by constructing protein-protein interaction(PPI) networks. Methods:Gene chip expression data were obtained from GEO database, and the DEGs were screened by GEO2 R tool;PPI network was constructed by STRING database and Cytoscape software, and relevant characteristic genes and signal pathway information were obtained by DAVID enrichment. Results:A total of 481 DEGs were obtained by microarray analysis. Compared with sensitive cell lines, 418 genes were up-regulated and 63 genes were down-regulated in cisplatin resistant cell lines. The DEGs were mainly enriched in piRNA metabolism, DNA methylation modification, cell mitosis and cell cycle progression etc. The protein complex was predicted to have 6 main functional clusters, which were respectively related to chemokine,keratinization, piRNA metabolism, cytokine receptor interaction, cytokine secretion regulation and chromatin silencing related biological processes. Conclusion:In this study, bioinformatics methods were used to find the characteristic genes and signaling pathways of cisplatin resistant cell lines, among which the significantly up-regulated genes such as SAA1, KRT5, TDRD9, BCL2 A1,CSF1 R and HIST1 H1 A and their functional groups may be the potential molecular mechanism of cisplatin resistance in NSCLC,providing a new theoretical basis for clinical precision therapy.
作者
朱立
戴五敏
卢德赵
ZHU Li;DAI Wumin;LU Dezhao(College of Life Sciences,Zhejiang Chinese Medical University,Hangzhou 310053,Zhejiang,China;Medical Engineering Department,The Cancer Hospital of the University of Chinese Academy of Sciences,Institute of Basic Medicine and Cancer,Chinese Academy of Sciences,Hangzhou 310022,Zhejiang,China;Experimental Research Center,The Cancer Hospital of the University of Chinese Academy of Sciences,Institute of Basic Medicine and Cancer,Chinese Academy of Sciences,Hangzhou 310022,Zhejiang,China)
出处
《中国肿瘤生物治疗杂志》
CAS
CSCD
北大核心
2020年第11期1278-1283,共6页
Chinese Journal of Cancer Biotherapy
基金
浙江省自然科学基金/青年基金资助项目(No.LQ19H160004)。
关键词
非小细胞肺癌
顺铂耐药
差异基因
生物信息学分析
non-small cell lung cancer(NSCLC)
cisplatin resistance
dfferential gene
bioinformatics analysis
