Cell division cycle 6 ​is an independent prognostic biomarker in breast cancer.

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-stage ​BC. CDC6 messenger RNA (mRNA) 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 and 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 outcome [p=0.007; hazard ratio (HR)=1.3; 95% confidence interval (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.