Screening crucial genes involved in triple-negative breast cancer through bioinformatics analysis of microarray data

摘要

Purpose: Triple-negative breast cancer (TNBC) is breast cancer with estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) negative. TNBC patients have a high risk of distant recurrence and death. This study aimed to investigate the mechanisms of TNBC. Materials and Methods: GSE38959 downloaded from Gene Expression Omnibus database included 30 TNBC cells and 13 normal mammary gland ductal cells. The differentially expressed genes (DEGs) were identified using limma package in a bioconductor and then annotated. Using the Database for Annotation. Visualization and Integrated Discovery (DAVID) tool, their functions were predicted through enrichment analysis. After the protcin-protein interaction (PPI) interactions were searched using STRING database, PPI network and modules were constructed by Cytoseape software. Results: A total of 2,039 DEGs were identified in TNBC cells. Among the uprcgulated genes, there were 36 TFs and 78 TAGs. Among the downregulated genes, a total of 46 TFs and 89 TAGs were annotated. Three significant modules were identified from the PPI network for the DEGs. Enrichment analysis showed that CCNB1. CDK1. PLK1, BUB1. and BUB1B were enriched in cell cycle, meanwhile, PSMD4 was enriched in the pro-teasomc pathway. Genes might also function in TNBC through interacting with others (e.g. CDK1-CCNB1, PSMD14-UCHL5, BUB 1 - PLK 1. and BUB 1 -BUB 1 B). Conclusion: In conclusion. CDK 1 and CCNB1 were the key genes involved in the proliferation and apoptosis of TNBC cells. BUB1. BUBR1, and PLK1 might play crucial roles in the chromosomal instability in TNBC development. The interaction between UCHL5 and PSMD14 might be the pivotal mechanism in the degradation of HR in TNBC.