Prognostic and clinical significance of the proliferation marker MCM7 in breast cancer

Lashen, Ayat G.; Toss, Michael S.; Rutland, Catrin S.; Green, Andrew R.; Mongan, Nigel P.; Rakha, Emad

Abstract

Introduction: Minichromosome maintenance complex component 7 (MCM7) plays an essential role in proliferation and DNA replication of cancer cells. However, the expression and prognostic significance of MCM7 in breast cancer (BC) remain to be defined. In this study, we aimed to evaluate the role of MCM7 in BC. Methods: We conducted immunohistochemistry staining of MCM7 in 1156 operable early-stage BC samples and assessed MCM7 at the transcriptomic levels using publicly available cohorts (n=13,430). MCM7 expression was evaluated and correlated with clinicopathological parameters including Ki67 labelling index and patient outcome. Results: At the transcriptomic level, there was a significant association between high MCM7 mRNA levels and shorter patient survival in the whole cohort and in luminal BC class but not in the basel-like molecular subtype. High MCM7 protein expression was detected in 43% of patients and was significantly associated with parameters characteristic of aggressive tumour behaviour. MCM7 was independently associated with shorter survival, particularly in estrogen receptor-positive (luminal) BC. MCM7 stratified luminal tumours with aggressive clinicopathological features into distinct prognostic groups. In endocrine therapy treated BC patients, high MCM7 was associated with poor outcome but such association disappeared with administration of adjuvant chemotherapy. Patients with high expression of Ki67 and MCM7 showed worst survival while patients with double low expression BC showed the best outcome compared with single expression groups. Conclusion: The current findings indicate that MCM7 expression has a prognostic value in BC and can be used to identify luminal BC patients who can benefit from adjuvant chemotherapy.

Citation

Lashen, A. G., Toss, M. S., Rutland, C. S., Green, A. R., Mongan, N. P., & Rakha, E. (2024). Prognostic and clinical significance of the proliferation marker MCM7 in breast cancer. Pathobiology, https://doi.org/10.1159/000540790

• Journal Article Type: Article
• Acceptance Date: Aug 5, 2024
• Online Publication Date: Aug 27, 2024
• Publication Date: Aug 27, 2024
• Deposit Date: Aug 16, 2024
• Publicly Available Date: Sep 17, 2024
• Journal: Pathobiology
• Print ISSN: 1015-2008
• Electronic ISSN: 1423-0291
• Publisher: Karger Publishers
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1159/000540790
• Keywords: Breast cancer; MCM7; endocrine; prognosis; molecular classes
• Public URL: https://nottingham-repository.worktribe.com/output/38382936
• Publisher URL: https://karger.com/pat/article/doi/10.1159/000540790/912413/Prognostic-and-Clinical-Significance-of-the