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Screening of potential hub genes and key pathways associated with breast cancer by bioinformatics tools

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Breast cancer (BC) remains the leading cause of cancer-related death in women worldwide. The development of new targeted therapies that may improve patient survival remains an area of growing interest.… Click to show full abstract

Breast cancer (BC) remains the leading cause of cancer-related death in women worldwide. The development of new targeted therapies that may improve patient survival remains an area of growing interest. This study aimed to identify new biomarkers involved in BC progression that could be used as potential targeted therapies. DEGs were selected from three gene expression profiles, GSE55715, GSE124646, and GSE87049, using the GEO2R tool and Venn diagram software. Gene Ontology and KEGG pathways were then performed using DAVID software. Next, the PPI network was constructed using STRING and visualized using Cytoscape software, and hub genes were extracted using the cytoHubba plug-in. Survival analysis was performed using the Kaplan–Meier Plotter, while the expression of hub genes in BC was verified using the GEPIA2 tool. Finally, transcription the factors of hub genes were determined using the NetworkAnalyst database, and the TIMER tool was employed to explore the infiltration levels of tumor immune cells with related genes. A total of 146 DEGs were identified in the three datasets, including 60 upregulated genes that were enriched in the cell cycle, and 86 downregulated genes that were mainly enriched in the TNF signaling pathway and pathways in cancer. Ten genes were identified: BUB1, CDK1, HMMR, MAD2L1, CEP55, AURKA, CCNB2, TPX2, MELK, and KIF20A. The overexpression of hub genes, except CDK1, was associated with poor survival in BC and was regulated by several transcription factors involved in DNA binding activity and transcription regulation. The infiltration levels of immune cells were positively correlated with hub genes, particularly macrophages and CD4+ T cells. This study identified new reliable molecular biomarkers that can serve as potential therapeutic targets for BC treatment.

Keywords: screening potential; hub genes; breast cancer; cancer

Journal Title: Medicine
Year Published: 2023

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