Retrospective assessment of cyclin-dependent kinase 5 mRNA and protein expression and its association with patient survival in breast cancer.

Abstract

Cyclin-dependent kinase 5 (Cdk5) is an atypical member of the cyclin-dependent kinase family and functions as a serine/threonine kinase that can be activated by non-cyclin binding activators p35 or p39. Cdk5 expression and activity has been linked with the development and progression of cancer; however, its expression in breast cancer has not been fully described. Protein expression of Cdk5 was determined in a large cohort of early-stage invasive breast cancer tumours (n = 1110) with long-term follow-up data using immunohistochemistry. Expression of CDK5 mRNA was assessed in the METABRIC cohort (n = 1980). Low nuclear and cytoplasmic expression of Cdk5 expression was significantly associated with shorter breast cancer-specific survival (P = .004 and P = .001, respectively). Importantly, low nuclear and cytoplasmic expression of Cdk5 remained associated with survival in multivariate analysis, including potentially confounding factors (hazard ratio (HR) = 0.612, 95% confidence interval (CI) = 0.418-0.896, P = .011 and HR = 0.507, 95% CI = 0.318-0.809, P = .004, respectively). In addition, low nuclear and cytoplasmic expression of Cdk5 was significantly associated with clinicopathological criteria associated with adverse patient prognosis. Low CDK5 mRNA expression was associated with shorter patient survival (P = .005) in the METABRIC cohort; no associations between copy gain or loss and survival were observed. These data suggest that low Cdk5 expression is associated with poor clinical outcome of breast cancer patients and may be of clinical relevance.

• Authors: Behnaz Saidy, Emad A Rakha, Andrew R Green, Ian O Ellis, Stewart G Martin, Sarah J Storr
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 24 Issue 11 Pg. 6263-6271 (06 2020) ISSN: 1582-4934 [Electronic] England
• PMID: 32352232 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• Dopamine and cAMP-Regulated Phosphoprotein 32
• PPP1R1B protein, human
• RNA, Messenger
• Receptors, Estrogen
• Cyclin-Dependent Kinase 5

Topics

• Breast Neoplasms (genetics, pathology)
• Cohort Studies
• Cyclin-Dependent Kinase 5 (genetics, metabolism)
• Dopamine and cAMP-Regulated Phosphoprotein 32 (genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Kaplan-Meier Estimate
• Middle Aged
• Neoplasm Invasiveness
• RNA, Messenger (genetics, metabolism)
• Receptors, Estrogen (metabolism)
• Retrospective Studies
• Survival Analysis