Overexpression of Uridine-Cytidine Kinase 2 Correlates with Breast Cancer Progression and Poor Prognosis.

PURPOSE

Uridine-cytidine kinase (UCK) 2 is a rate-limiting enzyme involved in the salvage pathway of pyrimidine-nucleotide biosynthesis. Recent studies have shown that UCK2 is overexpressed in many types of cancer and may play a crucial role in activating antitumor prodrugs in human cancer cells. In the current study, we evaluated the potential prognostic value of UCK2 in breast cancer.

METHODS

We searched public databases to explore associations between gene expression and clinical parameters in patients with breast cancer. Gene set enrichment analysis (GSEA) was performed to identify biological pathways associated with gene expression levels. Survival analyses were performed using 10 independent large-scale breast cancer microarray datasets.

RESULTS

We found that mRNA expression was elevated in breast cancer tissue compared with adjacent nontumorous tissue or breast tissue from healthy controls. High levels were correlated with estrogen receptor negativity (<0.001), advanced tumor grade (<0.001), and poor tumor differentiation (<0.001). GSEA revealed that -high breast cancers were enriched for gene sets associated with metastasis, progenitor-like phenotypes, and poor prognosis. Multivariable Cox proportional hazards regression analyses of microarray datasets verified that high gene expression was associated with poor overall survival in a dose-response manner. The prognostic power of was superior to that of TNM staging and comparable to that of multiple gene signatures.

CONCLUSION

These findings suggest that may be a promising prognostic biomarker for patients with breast cancer.