乳腺癌他莫昔芬耐药相关基因及通路的筛选  

Identification of keygenes and pathwaysoftamoxifen-resistancein breast cancer

作　　者：柴慈曼 杨绍时[1] CHAI Ci-man;YANG Shao-shi(Department of Thyroid and Breast Surgery,The Second Hospital,Tianjin Medical University,Tianjin 300211,China)

机构地区：[1]天津医科大学第二医院甲状腺乳腺外科,天津300211

出　　处：《天津医科大学学报》2018年第6期501-504,512,共5页Journal of Tianjin Medical University

基　　金：天津医科大学第二医院青年基金项目资助(2017ydey05)

摘　　要：目的:利用美国国家生物技术信息中心基因表达数据库中雌激素受体阳性乳腺癌表达谱芯片进行生物信息学分析,筛选他莫昔芬耐药的关键基因和信号通路。方法:利用基因芯片GSE26459,R软件分析得到差异基因,DAVID进行Gene Ontology和KEGG富集分析,STRING绘制蛋白作用网络。GSEA富集分析得到耐药相关通路及基因。结合蛋白作用网络筛选目标基因并验证。结果:筛选出差异基因1 516个,上调基因505个,下调基因624个。通路富集分析发现脂肪酸代谢通路、细胞粘附、胰岛素抵抗等信号通路在乳腺癌的他莫昔芬耐药中起重要作用,并在富集通路中筛选出ACSL1等候选目标基因并验证。结论:利用生物信息学有效分析他莫昔芬耐药的基因芯片数据,为他莫昔芬耐药的治疗靶点提供重要依据。Objective： To screen and explore the candidate genes and the molecular signaling pathwaysoftamoxifen resistance in ER- positive breast cancerbased on the Gene Expression Omnibus （GEO）. Methods： Differentially expressed genes （DEGs） were identified in tamoxifen-sensitive samples and were compared with tamoxifen-resistance samples based on the microarray GSE26459usingthe R software,and then were subjected togene ontology enrichment analysisand pathway enrichment analysis by DAVID database. In addition, we analyzed the protein protein interaction（PPI） network of DEGs with Search Tool for the Retrieval of Interacting Genes （STRING） database. Western-blot verified the expression of the candidate gene. Results： There were 1 516 DEGs between in tamoxifen-sensitive and resistance breast cancer, which contained 505up-regulated and 624 down-regulated genes. GO categories andKEGG analysis showed DEGs were mainly enriched inFatty acid metabolism,cell adhesion, and insulin resistance pathways. ACSL1 might be the key gene in the enriched pathways. Conclusion： The study may provide some basis of for treatment of tamoxifen-resistance breast cancerby bioinformatics analysis.

关 键 词：他莫昔芬耐药 乳腺癌 生物信息学 

分 类 号：R737.9[医药卫生—肿瘤]