Identification of potential key genes and pathways in Triple-negative breast cancer using bioinformatics analysis

Triple-negative breast cancer(TNBC) refers to breast cancer that does not express estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor ۲ (Her۲). Due to the lack of these receptors, no targeted agents have shown broad effectiveness against TNBC, therefore, there is a critical need for more active therapeutic strategies. This study aimed to identify differentially expressed genes (DEGs) for TNBC and elucidate the potential interactions among them. Microarray dataset GSE۶۲۹۳۱ was selected from GEO database, which composed of gene expression data from ۱۰۰ samples, including ۵۳ non-TNBC and ۴۷ TNBC. The differentially expressed genes (DEGs) with adj P.value <۰.۰۱ and |LogFC|≥۱.۵ were identified using GEO۲R. The GO and KEGG analyses were conducted through Enrichr. The protein-protein interaction (PPI) network of the DEGs was established through STRING website, visualized by Cytoscape and further analyzed by MCODE. CytoHubba was used to identify hub genes. ۱۷۶ up-regulated and ۲۱۷ down-regulated DEGs were identified. These significantly changed genes are mainly involved in the biological process termed response to estradiol, cellular response to estradiol stimulus and nervous system development. Protein digestion and absorption and regulation of lipolysis in adipocytes were the major enriched pathways for the up-regulated and down-regulated genes, respectively. FOXM۱, EGR۱ and RNF۲ were the top transcription factors controlling the expression of up regulated genes. Hub genes selected, included KIF۲C, KIF۲۰A, CCNA۲, NDC۸۰, AURKB and BUB۱. These pathways and genes identified could help to understand the mechanism of development of TNBC and might be promising targets for the TNBC treatment.

کلیدواژه ها:

Transcription factors (TFs) ، Signaling pathway ، Biological process ، Hub genes