The expression and prognostic value of minichromosome maintenance markers in human breast cancer: a comprehensive analysis

Abstract

Objective: Breast cancer (BC) is one of the most health-threatening neoplasms for women worldwide. Despite advances in detection and treatment strategies over the past few decades, the current biomarkers of BC are less than satisfactory for effective prognosis and individualized treatment. This study aimed to investigate the new biomarkers to meet this urgent demand. Methods: The current study investigated the transcriptional levels of minichromosome maintenance genes (MCMs) in BC patients from the Oncomine, UALCAN database, and Gene Expression Profiling Interactive Analysis (GEPIA); protein expression levels of MCM proteins in BC patients were derived from the Human Protein Atlas (HPA) database. Further, survival analysis was evaluated with Kaplan-Meier Plotter. BC genome atlas data were obtained from cBioPortal databases. Gene regulatory network analysis was performed using the STRING online tool, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using DAVID. Results: Based on multiple database analysis, mRNA and protein levels of MCM2, MCM4 and MCM10 were much higher in BC patient, and survival analysis showed that high transcription levels of most MCMs were found to be associated with poor prognosis for BC patients; moreover, the MCMs genetic alterations, especially of MCM2, MCM4 and MCM10, were found in 45% of BC patients. In addition, dysregulation of MCMs was considered to possibly affect DNA damage/repair, cell cycle dysregulation and chromosome instability. Conclusions: In summary, this study indicated that MCM2, MCM4, and MCM10 are potential prognostic markers and therapeutic targets for BC.