Identification of the key pathways and genes involved in HER2-positive breast cancer with brain metastasis

Abstract

BackgroundThe risk of brain metastasis (BM) in HER2-positive (+) breast cancer (BC) patients is significantly higher than that in HER2-negative (-) BC patients. The high incidence and mortality rate makes it urgent to elucidate the key pathways and genes involved and identify patients who are more at risk of developing BM. Materials and methodsTo identify the target genes in HER2+BC patients with BM, we analyzed the microarray datasets (GSE43837) derived from the Gene Expression Omnibus (GEO) database. The GEO2R tool was used to extract the differentially expressed genes (DEGs) involved in HER2+ primary BC and BC with BM. Bioinformatics methods including Gene Ontology (GO) functional annotation analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed with the screened DEGs. The protein-protein interactions of the DEGs were analyzed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized using Cytoscape software. Finally, GSEA analysis was performed to identify the hub genes and the important pathways. ResultsA total of 751 upregulated and 285 downregulated DEGs were identified. The GO function and KEGG pathway enrichment analyses indicated that the DEGs were all enriched in the protein binding molecular function. The top five hub nodes were screened out, included PHLPP1, UBC, ACACB, TGFB1, and ACTB. The GSEA results demonstrated that the five hub genes are mainly enriched in the ribosomal pathway. ConclusionOur study suggests that the five hub genes (PHLPP1, UBC, ACACB, TGFB1, and ACTB) are associated with HER2+BC with BM. The GSEA analysis revealed that the ribosomal pathway seems to play a very important role in the pathogenesis of HER2+BC with BM.