Liu Zihao, Liang Gehao, Tan Luyuan, Su A N, Jiang Wenguo, Gong Chang
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetic and Gene Regulation, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, P.R. China.
Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff University, Cardiff, U.K.
Anticancer Res. 2017 Aug;37(8):4329-4335. doi: 10.21873/anticanres.11826.
BACKGROUND/AIM: The aim of the present study was to identify key pathways and genes in breast cancer and develop a new method for screening key genes with abnormal expression based on bioinformatics.
Three microarray datasets GSE21422, GSE42568 and GSE45827 were downloaded from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were analyzed using GEO2R. The gene ontology (GO) and pathway enrichment analysis were established through DAVID database. The protein-protein interaction (PPI) network was performed through the Search Tool for the Retrieval of Interacting Genes (STRING) database and managed by Cytoscape. The overall survival (OS) analysis of the 4 genes including AURKA, CDH1, CDK1 and PPARG that had higher degrees in this network was uncovered Kaplan-Meier analysis.
A total of 811 DEGs were identified in breast cancer, which were enriched in biological processes, including cell cycle, mitosis, vessel development and lipid metabolic. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the up-regulated DEGs were particularly involved in cell cycle, progesterone-mediated oocyte maturation and leukocyte transendothelial migration, while the down-regulated DEGs were mainly involved in regulation of lipolysis, fatty acid degradation and glycerolipid metabolism. Through PPI network analysis, 14 hub genes were identified. Among them, the high expression of AURKA, CDH1 and CDK1 were associated with worse OS of breast cancer patients; while the high expression of PPARG was linked with better OS.
The present study identified key pathways and genes involved in breast cancer which are potential molecular targets for breast cancer treatment and diagnosis.
背景/目的:本研究旨在识别乳腺癌中的关键通路和基因,并基于生物信息学开发一种筛选异常表达关键基因的新方法。
从基因表达综合数据库(GEO)下载三个微阵列数据集GSE21422、GSE42568和GSE45827,并使用GEO2R分析差异表达基因(DEG)。通过DAVID数据库进行基因本体(GO)和通路富集分析。通过检索相互作用基因的搜索工具(STRING)数据库构建蛋白质-蛋白质相互作用(PPI)网络,并由Cytoscape管理。对该网络中度数较高的AURKA、CDH1、CDK1和PPARG这4个基因进行总生存(OS)分析,采用Kaplan-Meier分析。
在乳腺癌中总共鉴定出811个DEG,这些基因富集于生物过程,包括细胞周期、有丝分裂、血管发育和脂质代谢。京都基因与基因组百科全书(KEGG)通路分析显示,上调的DEG特别参与细胞周期、孕酮介导的卵母细胞成熟和白细胞跨内皮迁移,而下调的DEG主要参与脂肪分解调节、脂肪酸降解和甘油脂质代谢。通过PPI网络分析,鉴定出14个枢纽基因。其中,AURKA、CDH1和CDK1的高表达与乳腺癌患者较差的OS相关;而PPARG的高表达与较好的OS相关。
本研究鉴定出参与乳腺癌的关键通路和基因,它们是乳腺癌治疗和诊断的潜在分子靶点。