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.

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