mRNA Expression of CDK2AP1 in Human Breast Cancer: Correlation with Clinical and Pathological Parameters

Background: Cyclin-dependent kinase 2-associated protein 1 (CDK2AP1) interacts with CDK2AP2, modulates the actions of transforming growth factor-B1, cyclin-dependent kinase 2 and retinoblastoma protein, and closely interacts with micro-RNA21 and micro-RNA25. Our objective was to determine if CDK2AP1 mRNA expression levels were consistent with tumour-suppressive functions in breast cancer. Materials and Methods: A total of 134 samples were analysed. CDK2AP1 mRNA levels were measured using quantitative polymerase chain reaction (RT-PCR) and normalised against glyceraldehyde 3-phosphate dehydrogenase mRNA. Levels in breast cancer and adjacent non-cancerous breast tissue were analysed against pathological and clinical parameters (TNM staging, survival over a 10-year follow-up period). Results: Normalised CDK2AP1 expression was 38-fold higher in adjacent non-cancerous breast tissue than in breast cancer. CDK2AP1 expression in disease-free patients at 10 years was more than threefold that of patients who died of breast cancer. However, neither of these differences in expression levels reached statistical significance. CDK2AP1 mRNA levels were higher in TNM1 compared to TNM3 (p=0.016) and with TNM4 (p=0.016). There were no significant associations between CDK2AP1 expression and estrogen receptor status, tumour grade and tumour type. There was no significant difference in overall survival between patients with high and those with low CDK2AP1 mRNA levels after a median follow-up of 10 years (Kaplan-Meier analysis, p=0.872). Conclusion: To our knowledge, this is the first study in the literature to examine the mRNA expression of CDK2AP1 in human breast cancer over a long-term follow-up period. A compelling relationship exists between high CDK2AP1 mRNA expression and lower TNM classification of breast cancer, which is consistent with CDK2AP1 having a tumour-suppressive function.