乳腺癌拉帕替尼耐药关键基因的生物信息学研究  

Bioinformatics analysis of hub genes for lapatinib resistance in breast cancer

作　　者：吴淑菲 谭巧 张超[1] 夏术森 弋鹏圣[1,2] 侯令密 WU Shufei;TAN Qiao;ZHANG Chao;XIA Shusen;YI Pengsheng;HOU Lingmi(Department of General Surgery 1,Yingshan Hospital,West China Hospital,Sichuan University,Nanchong,Sichuan 637000,P.R.China;Academician(Expert)Workstation,Laboratory of Biological Targeting of Breast Cancer,Affiliated Hospital of North Sichuan Medical University,Nanchong,Sichuan 637000,P.R.China)

机构地区：[1]四川大学华西医院营山医院普通外科,四川南充637000 [2]川北医学院附属医院院士(专家)工作站乳腺癌生物靶向研究室,四川南充637000

出　　处：《中国普外基础与临床杂志》2022年第3期337-344,共8页Chinese Journal of Bases and Clinics In General Surgery

基　　金：南充市市校合作科研创新团队建设专项(项目编号:20SXCXTD0001)。

摘　　要：目的通过生物信息学方法筛选乳腺癌拉帕替尼耐药的关键基因和通路,为进一步研究奠定基础。方法从美国国家生物信息中心的GEO数据库筛选并下载GSE16179和GSE38376基因表达谱数据,归一化处理后使用R语言的limma包分析和筛选差异表达基因(differential expressed genes,DEGs);利用DAVID在线数据库对DEGs进行功能和通路富集;使用STRING在线工具及Cytoscape软件建立蛋白互相作用网络(proteinprotein interaction network,PPI),并利用MCODE插件分析得到关键模块和基因;应用DAVID和GeneMANIA对关键基因进行功能富集与共表达网络分析;用Kaplan-Meier Plotter在线数据库对关键基因进行生存预后分析。结果共筛选出206个DEGs,其中上调基因126个、下调基因80个;DAVID分析结果显示,DEGs主要富集在细胞外空间和区域,包括细胞外基质组织、氧结合、整合素结合、细胞黏附、血管生成的正调控、Hippo信号通路、转化生长因子-β信号通路等生物过程;PPI网络可视化得到74个节点,应用MCODE插件筛选得到10个关键基因。基于Kaplan-Meier Plotter在线数据库的生存分析发现,其中6个关键基因(过氧化物酶体增殖物激活受体γ、转化生长因子β受体2、基质金属蛋白酶抑制剂1、转化生长因子β诱导因子、丝氨酸蛋白酶抑制剂E1和血小板凝血酶蛋白1)与乳腺癌患者的预后密切相关(P<0.05)。结论本研究筛选出的6个基因可能在拉帕替尼治疗乳腺癌耐药中起重要作用。Objective To screen the lapatinib resistance-related hub genes of breast cancer by bioinformatics initially in order to lay the foundation for further study.Methods We screened and downloaded the gene expression profile data of GSE16179 and GSE38376 from the gene expression omnibus(GEO),and used the limma package of R software to identify the differential expressed genes(DEGs)in breast cancer cells.Then we used the DAVID online website for pathway and function enrichment.With the usage of STRING and Cytoscape,the protein-protein interaction network(PPI)was constructed,and the plug-in app MCODE in Cytoscape was applied to screen hub genes.Then we performed the function enrichment and co-expression analysis of hub genes by DAVID and GeneMANIA.Kaplan-Meier Plotter was used to conduct survival analysis of hub genes.Results A total of 206 kinds of DEGs were screened,and there were 126 kinds of up-regulated genes and 80 kinds of down-regulated genes.DAVID results showed that DEGs were mainly enriched in the biological processes of extracellular space and extracellular region,including extracellular matrix organization,oxygen binding,integrin binding,cell adhesion,positive regulation of angiogenesis,Hippo signaling pathway,transforming growth factor-βsignaling pathway and so on.PPI network visualized 74 nodes,the top 10 kinds of hub genes with high connectivity in the gene expression network were screened by MCODE.The Kaplan-Meier Plotter analysis confirmed that 6 of the 10 kinds of hub genes,including peroxisome proliferator activated receptor gamma,transforming growth factor beta receptor 2,tissue inhibitor of metalloproteinase 1,transforming growth factor beta induced,serpin family E member 1,and thrombospondin 1,were correlated with the prognosis of breast cancer patients.Conclusion This 6 kinds of genes may play a significant role in lapatinib resistance of breast cancer.

关 键 词：乳腺癌 生物信息学 拉帕替尼耐药 关键基因 

分 类 号：R737.9[医药卫生—肿瘤] Q811.4[医药卫生—临床医学]