Identification of hub genes and small molecule therapeutic drugs related to breast cancer with comprehensive bioinformatics analysis.

Abstract

Breast cancer is one of the most common malignant tumors among women worldwide and has a high morbidity and mortality. This research aimed to identify hub genes and small molecule drugs for breast cancer by integrated bioinformatics analysis. After downloading multiple gene expression datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, 283 overlapping differentially expressed genes (DEGs) significantly enriched in different cancer-related functions and pathways were obtained using LIMMA, VennDiagram and ClusterProfiler packages of R. We then analyzed the topology of protein–protein interaction (PPI) network with overlapping DEGs and further obtained six hub genes (RRM2, CDC20, CCNB2, BUB1B, CDK1, and CCNA2) from the network via STRING and Cytoscape. Subsequently, we conducted genes expression verification, genetic alterations evaluation, immune infiltration prediction, clinicopathological parameters analysis, identification of transcriptional and post-transcriptional regulatory molecules, and survival analysis for these hub genes. Meanwhile, 29 possible drug candidates (e.g., Cladribine, Gallium nitrate, Alvocidib, 1β-hydroxyalantolactone, Berberine hydrochloride, Nitidine chloride) were identified from the DGIdb database and the GSE85871 dataset. In addition, some transcription factors and miRNAs (e.g., E2F1, PTTG1, TP53, ZBTB16, hsa-miR-130a-3p, hsa-miR-204-5p) targeting hub genes were identified as key regulators in the progression of breast cancer. In conclusion, our study identified six hub genes and 29 potential drug candidates for breast cancer. These findings may advance understanding regarding the diagnosis, prognosis and treatment of breast cancer.