影响三阴性乳腺癌对化疗敏感性的分子靶标筛选  

Identification of molecular targets in the response of triple negative breast cancer to chemotherapy

作　　者：李静[1] 茹沙洪 

机构地区：[1]中国医学科学院北京协和医学院生物医学工程研究所,天津300192

出　　处：《国际生物医学工程杂志》2015年第5期278-281,I0006,共5页International Journal of Biomedical Engineering

基　　金：天津市科技型中小企业技术创新基金项目（13ZXCXSY15900）

摘　　要：目的探索影响三阴性乳腺癌（TNBC）对化疗敏感性的分子靶标及机制，为TNBC中基于基因检测的化疗方案提供重要依据。方法采用美国国家生物技术中心（NCBI）关于TNBC对化疗敏感性研究的基因表达谱数据（GSE43502），利用R编程语言对表达谱数据进行预处理，得到化疗后复发的TNBC患者相对于未复发患者的差异表达基因；基于DAVID数据库对差异表达基因进行功能富集分析，通过starBase数据库筛选出可能调控差异表达基因的miRNA，利用Cytoscape构建miRNA-基因调控网络。结果得到了312个差异表达基因，它们主要富集于细胞膜结构、金属离子稳态等生物过程及与免疫和炎症相关的通路；筛选了171个可能调控差异表达基因的miRNA，它们与差异表达基因构成了553个miRNA-基因调控关系对。结论hsa—miR。30d．5p、SIX4等可能通过影响细胞结构或者免疫系统来调节TNBC对化疗的敏感性。Objective To explore the molecular targets and mechanisms that could influence the sensitivity of triple negative breast cancer （TNBC） to chemotherapy, to provide important references for the chemotherapy based on gene detection. Methods The gene expression dataset GSE43502 was downloaded from the Gene Expression Omnibus in National Center for Biotechnology Information （NCBI）. Gene expression data preprocessing was conducted by R Programming. The differentially expressed genes in the TNBC patients that relapsed after chemotherapy compared with the non-relapsed ones were obtained. Besides, the Database for Annotation Visualization and Integrated analysis （DAVID） was used for functional analysis of those genes. The microRNA （miRNA） that might regulate the differentially expressed genes was obtained from the starBase database. Furthermore, Cytoscape was used for the construction of miRNA-gene regulation network. Results Three hundred and twelve differentially expressed genes were obtained. Some biological process related to cell membrane, metal ion homeostasis and pathways involved in immune and inflammatory were found to be enriched in those genes. Furthermore, 171 miRNA that might regulate the differentially expressed genes were obtained and 553 miRNA-gene regulation pairs were formed. Conclusions hsa-miR-30d-Sp, SIX4, etc. might influence the sensitivity of TNBC to chemotherapy through cell structure or immune system.

关 键 词：三阴性乳腺癌 化疗 功能富集分析 MIRNA 

分 类 号：R737.9[医药卫生—肿瘤]