摘要
目的使用生物信息学方法分析耐吉非替尼非小细胞肺癌(NSCLC)细胞的差异表达基因。方法使用GEO数据库下载GSE122005数据集,包括3份吉非替尼敏感细胞样本(Gefitinib1、Gefitinib2、Gefitinib3)和3份获得性吉非替尼耐药细胞样本(Acquired1、Acquired2、Acquired3)。对数据质量进行检测后,使用R语言筛选差异表达基因。利用在线工具DAVID 6.7和KOBAS 3.0对差异表达基因进行富集分析和通路分析。使用STRING 11.0构建蛋白质互相作用(PPI)网络,通过CytoScape 3.7.1筛选关键基因。针对不同关键基因表达水平的NSCLC患者,利用在线工具Kaplan-Meier Plotter进行生存分析。结果共筛选出604个差异表达基因,包括上调基因332个,下调基因272个。差异表达基因主要涉及9种分子功能(包括生长因子结合、糖蛋白结合等)、17种细胞组成(包括核小体、细胞外空隙、细胞外区域部分、质膜部分等)、72种生物过程(包括核小体装配、创伤反应等),参与癌症中的转录失调、肿瘤坏死因子信号通路等。PPI网络筛选出10个关键基因(CXCL8、ERBB2、TIMP1、SPP1、CXCL1、CDH2、CCL2、EDN1、CSF2、CCL20);CXCL8、SPP1、TIMP1高表达和EDN1低表达的NSCLC患者生存期较短(均P<0.05)。结论 CXCL8、SPP1、TIMP1、EDN1可能在NSCLC对吉非替尼耐药的机制中起重要作用,但具体的作用机制有待进一步研究。
Objective To analyze the differentially expressed genes in Gefitinib-resistant non-small cell lung cancer(NSCLC)cells by using bioinformatics analysis.Methods Data set GSE122005 was obtained from GEO database,including three samples of Gefitinib-sensitive cells(Gefitinib1,Gefitinib2,and Gefitinib3)and three samples of acquired Gefitinib-resistant cells(Acquired1,Acquired2,and Acquired3).After data quality detection,differentially expressed genes were screened based on R Language.Online tools DAVID6.7 and KOBAS 3.0 were applied to enrich ment analysis and pathway analysis on the differentially expressed genes.Protein-protein interaction(PPI)network was established by STRING 11.0,then the key genes were screened through CytoScape 3.7.1.Survival analysis was conducted among NSCLC patients with different expression levels of key genes by online tool Kaplan-Meier Plotter.Results Totally 604 differentially expressed genes were obtained,consisting of 332 up-expression genes and 272 down-expression genes.The differentially expressed genes mainly involved nine molecular functions(including growth factor binding and glycoprotein binding),17 cellular components(including nucleosome,extracellular space,extracellular region part and plasma membrane part)and 72 biological processes(including nucleosome assembly and response to wounding),and participated in transcriptional misregulation in cancer and tumor necrosis factor signaling pathway,etc.Ten key genes(CXCL8,ERBB2,TIMP1,SPP1,CXCL1,CDH2,CCL2,EDN1,CSF2 and CCL20)were obtained from PPI network;shorter survival was found in NSCLC patients with highly expressed CXCL8,SPP1 or TIMP1,or in NSCLC patients with lowly expressed EDN1.Conclusion CXCL8,SPP1,TIMP1,and EDN1 may play an important role in mechanism of NSCLC resistance to Gefinitib,but further research on specific mechanism is required.
作者
黄溢问
吴凤
阳联
张文峰
贾家宝
孙易
庞伟毅
HUANG Yi-wen;WU Feng;YANG Lian;ZHANG Wen-feng;JIA Jia-bao;SUN Yi;PANG Wei-yi(School of Public Health,Guilin Medical University,Guilin 541000,China)
出处
《广西医学》
CAS
2021年第6期714-719,共6页
Guangxi Medical Journal
基金
广西自然科学基金(2013GXNSFBA019190,2014GXNSFCA118011)
大学生创新创业训练计划(201810601033)。
关键词
非小细胞肺癌
吉非替尼
耐药
差异表达基因
生物信息学
Non-Small cell lung cancer
Gefitinib
Drug resistance
Differentially expressed gene
Bioinformatics
