The Alterations and Potential Roles of MCMs in Breast Cancer.

Xinyu Liu,Ying Liu,Lingjun Feng,Siqi Song,Chunying Shi,Qiangshan Wang,Nicola Silvestris

doi:10.1155/2021/7928937

Abstract

The minichromosome maintenance (MCM) protein family plays a key role in eukaryotic DNA replication and has been confirmed to be associated with the occurrence and progression of many tumors. However, the expression levels, functions, and prognostic values of MCMs in breast cancer (BC) have not been clearly and systematically explained. In this article, we studied the transcriptional levels of MCMs in BC based on the Oncomine database. Kaplan-Meier plotter was used to analyze prognostic value of MCMs in human BC patients. Furthermore, we constructed a MCM coexpression gene network and performed functional annotation analysis through DAVID to reveal the functions of MCMs and coexpressed genes. The data showed that the expression of MCM2–8 and MCM10 but not MCM1 and MCM9 was upregulated in BC. Kaplan-Meier plotter analysis revealed that high transcriptional levels of MCM2, MCM4–7, and MCM10 were significantly related to low relapse-free survival (RFS) in BC patients. In contrast, high levels of MCM1 and MCM9 predicted high RFS for BC patients. This study suggests that MCM2, MCM4–7, and MCM10 possess great potential to be valuable prognostic biomarkers for BC and that MCM1 and MCM9 may serve as potential treatment targets for BC patients.

Highlights

Surveys show that breast cancer (BC) patients diagnosed worldwide are increasing, and BC is the most common carcinoma type in the female population [1, 2]
Our study showed that MCM2 was upregulated in BC and its upregulation was significantly associated with poor prognosis for BC patients
Our research found that the expression of MCM7 in BC was upregulated and significantly related to shorter relapse-free survival (RFS) in BC patients, revealing the prognostic value of MCM7 in BC patients

Summary

Introduction

Surveys show that breast cancer (BC) patients diagnosed worldwide are increasing, and BC is the most common carcinoma type in the female population [1, 2]. Classic clinical prognostic markers, such as progesterone receptor (PR), HER2, and estrogen receptor (ER) have played positive roles in endocrine therapy or targeted therapy in BC patients [4]. The roles of minichromosome maintenance (MCM) protein family members identified in human cancers have been widely reported. E MCM family plays important roles in the cell cycle and genome replication, including ten members: serum response factor (SRF, called MCM1) and MCM2–10 [5, 6]. MCMs are involved in the response of DNA damage [9, 10]. MCM interacts with cellular tumor antigen p53 binding protein 1 (53BP1) and Rad, and the consumption of MCM leads to a reduction in 53BP1 and Rad foci formed after DNA damage [10, 11]. The overexpression of MCM has been detected in various cancer tissues and cancer cell lines, including squamous cell lung carcinoma [12], kidney cancer [13], prostate carcinoma [14], BC [15], digestive system tumors [16,17,18], brain tumors [19], and lymphomas [20]

Methods

Findings

Discussion

Conclusion