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Cell division cycle 6 (CDC6) is an independent prognostic biomarker in breast cancer

Kariri, Yousif A.; Alsaleem, Mansour; Alhatlani, Bader Y.; Al-Kawaz, Abdulbaqi; Mongan, Nigel P.; Green, Andrew R.; Rakha, Emad A.

Authors

Yousif A. Kariri

Mansour Alsaleem

Bader Y. Alhatlani

Abdulbaqi Al-Kawaz

NIGEL MONGAN nigel.mongan@nottingham.ac.uk
Associate Pro-Vice Chancellorglobal Engagement

EMAD RAKHA Emad.Rakha@nottingham.ac.uk
Professor of Breast Cancer Pathology



Abstract

Cell division cycle 6 (CDC6) is a cell cycle protein involved in cell cycle control, DNA replication and cancer cell apoptosis. This study investigated the prognostic value of CDC6 in breast cancer (BC) utilising large well characterised cohorts of early-stages BC.
CDC6mRNA was assessed using the Molecular Taxonomy of the Breast Cancer International Consortium (n=1980), the Cancer Genome Atlas (n=854) and Kaplan–Meier Plotter (n=4,929) cohorts. CDC6 protein expression was evaluated using immunohistochemistry in a large (n=951) well-characterised Nottingham BC cohort. The associations between CDC6, clinicopathological parameters, molecular features and patient outcomes were assessed.
High CDC6 expression positively correlated with dysregulation of key BC-related genes, including gene involved in cell cycle, DNA damage repair, epithelial cell migration, and tumour microenvironment control as well as with markers characteristic of the basal-like phenotype (CK5, CK14, CK17). High CDC6 mRNA and protein expression were associated with clinicopathological parameters characteristic of aggressive behaviour, including high tumour grade, large tumour size, the presence of lymphovascular invasion and hormone receptor negativity. High CDC6 protein expression was an independent predictor of poor patients’ outcome (p=0.007; HR=1.3; 95% CI 1.2–1.9).
This study indicates that CDC6 is an independent prognostic biomarker in BC. These results warrant further functional validation for CDC6 as a potential therapeutic target in BC.

Citation

Kariri, Y. A., Alsaleem, M., Alhatlani, B. Y., Al-Kawaz, A., Mongan, N. P., Green, A. R., & Rakha, E. A. (2024). Cell division cycle 6 (CDC6) is an independent prognostic biomarker in breast cancer. Pathology, https://doi.org/10.1016/j.pathol.2024.09.006

Journal Article Type Article
Acceptance Date Sep 16, 2024
Online Publication Date Nov 14, 2024
Publication Date Nov 14, 2024
Deposit Date Sep 18, 2024
Publicly Available Date Nov 15, 2025
Journal Pathology
Print ISSN 0031-3025
Electronic ISSN 1465-3931
Publisher Lippincott, Williams & Wilkins
Peer Reviewed Peer Reviewed
DOI https://doi.org/10.1016/j.pathol.2024.09.006
Keywords CDC6; breast cancer; HER2; progression; prognosis; outcome
Public URL https://nottingham-repository.worktribe.com/output/39720412
Publisher URL https://www.sciencedirect.com/science/article/pii/S0031302524002940