Peng Cancan, Ma Wenli, Xia Wei, Zheng Wenling
Institute of Genetic Engineering, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Department of Clinical Laboratory, 421 Hospital of PLA, Guangzhou, Guangdong 510318, P.R. China.
Mol Med Rep. 2017 Mar;15(3):1087-1094. doi: 10.3892/mmr.2017.6101. Epub 2017 Jan 4.
Triple‑negative breast cancer (TNBC) is a heterogeneous disease characterized by an aggressive phenotype and reduced survival. The aim of the present study was to investigate the molecular mechanisms involved in the carcinogenesis of TNBC and to identify novel target molecules for therapy. The differentially expressed genes (DEGs) in TNBC and normal adjacent tissue were assessed by analyzing the GSE41970 microarray data using Qlucore Omics Explorer, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes. Pathway enrichment analyses for DEGs were performed using the Database for Annotation, Visualization and Integrated Discovery online resource. A protein‑protein interaction (PPI) network was constructed using Search Tool for the Retrieval of Interacting Genes, and subnetworks were analyzed by ClusterONE. The PPI network and subnetworks were visualized using Cytoscape software. A total of 121 DEGs were obtained, of which 101 were upregulated and 20 were downregulated. The upregulated DEGs were significantly enriched in 14 pathways and 83 GO biological processes, while the downregulated DEGs were significantly enriched in 18 GO biological processes. The PPI network with 118 nodes and 1,264 edges was constructed and three subnetworks were extracted from the entire network. The significant hub DEGs with high degrees were identified, including TP53, glyceraldehyde‑3‑phosphate dehydrogenase, cyclin D1, HRAS and proliferating cell nuclear antigen, which were predominantly enriched in the cell cycle pathway and pathways in cancer. A number of critical genes and pathways were revealed to be associated with TNBC. The present study may provide an improved understanding of the pathogenesis of TNBC and contribute to the development of therapeutic targets for TNBC.
三阴性乳腺癌(TNBC)是一种异质性疾病,具有侵袭性表型且生存率较低。本研究的目的是探讨TNBC发生发展的分子机制,并确定新的治疗靶点分子。通过使用Qlucore Omics Explorer、基因本体论(GO)和京都基因与基因组百科全书分析GSE41970微阵列数据,评估TNBC和癌旁正常组织中的差异表达基因(DEG)。使用在线资源注释、可视化和综合发现数据库对DEG进行通路富集分析。使用检索相互作用基因的搜索工具构建蛋白质-蛋白质相互作用(PPI)网络,并通过ClusterONE分析子网。使用Cytoscape软件可视化PPI网络和子网。共获得121个DEG,其中101个上调,20个下调。上调的DEG在14条通路和83个GO生物学过程中显著富集,而下调的DEG在18个GO生物学过程中显著富集。构建了具有118个节点和1264条边的PPI网络,并从整个网络中提取了三个子网。确定了具有高度的重要枢纽DEG,包括TP53、甘油醛-3-磷酸脱氢酶、细胞周期蛋白D1、HRAS和增殖细胞核抗原,它们主要富集在细胞周期通路和癌症相关通路中。揭示了许多关键基因和通路与TNBC相关。本研究可能有助于更好地理解TNBC的发病机制,并为TNBC治疗靶点的开发做出贡献。