Expression Profile and Prognostic Values of Mini-Chromosome Maintenance Families (MCMs) in Breast Cancer

BACKGROUND Mini-chromosome maintenance families (MCMs) were considered the key factors for DNA replication initiation. Emerging evidences indicate that MCM2-7 (MCMs) are highly expressed in tissues from various malignant tumors. However, little is known about the clinical values of MCMs in breast cancer. MATERIAL AND METHODS In our study, a comprehensive bioinformatics analysis was performed to investigate expression patterns, potential functions, and prognostic values of MCMs in breast cancer, through ONCOMINE, bc-GenExMiner v4.1, Kaplan-Meier Plotter, cBioPortal and GeneMANIA databases. RESULTS We found that mRNA levels of MCMs were significantly elevated in breast cancer, especially in fast-growing and spreading tumor subtypes. These over-expressed MCMs predicted worse prognosis for breast cancer patients with shorter relapse-free survival (RFS) and overall survival. Among these six factors, high expression of MCM2/4/5/7 significantly reduced the RFS for patients with Luminal-A or B breast cancer and elevated MCM6/7 indicated shorter RFS for patients with basal-like or HER2-positive breast cancer. We also found that genomic alteration of MCMs was frequently found in breast cancer and the most common alteration was mRNA upregulation and amplification. Furthermore, MCMs were highly correlated with CDC45, CDC7, TIMELESS, ORC6, MCM10, ORC5, ORC4 and ORC3, mainly functioning to control the DNA replication initiation and genome stability. CONCLUSIONS These results suggest that MCMs are attractive prognostic biomarkers for breast cancer. Our study also provides useful clinical information about the potential of MCMs as therapeutic targets.