Backgrounds: HER-2 positive breast cancer is a subtype of breast cancer with poor clinical outcome. The aim of this study was to identify differentially expressed genes (DEGs) for HER-2 positive breast cancer and elucidate the potential interactions among them.
Material and methods: Three gene expression profiles (GSE29431, GSE45827, and GSE65194) were derived from the Gene Expression Omnibus (GEO) database. GEO2R tool was applied to obtain DEGs between HER-2 positive breast cancer and normal breast tissues. Gene ontology (GO) annotation analysis and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis was performed by the Database for Annotation, Visualization and Integrated Discovery (David) online tool. Protein-protein interaction (PPI) network, hub gene identification and module analysis was conducted by Cytoscape software. Online Kaplan-Meier plotter survival analysis tool was also used to investigate the prognostic values of hub genes in HER-2 positive breast cancer patients.
Results: A total of 54 upregulated DEGs and 269 downregulated DEGs were identified. Among them, 10 hub genes including CCNB1, RAC1, TOP2A, KIF20A, RRM2, ASPM, NUSAP1, BIRC5, BUB1B, and CEP55 demonstrated by connectivity degree in the PPI network were screened out. In Kaplan-Meier plotter survival analysis, the overexpression of RAC1 and RRM2 were shown to be associated with an unfavorable prognosis in HER-2 positive breast cancer patients.
Conclusions: This present study identified a number of potential target genes and pathways which might impact the oncogenesis and progression of HER-2 positive breast cancer. These findings could provide new insights into the detection of novel diagnostic and therapeutic biomarkers for this disease.