Overexpression of uridine-cytidine kinase 2 correlates with breast cancer progression and poor prognosis

Guosong Shen, Pingya He, Yingying Mao, Peipei Li, Frank Luh, Guohui Ding, Xiyong Liu, Yun Yen

研究成果: 雜誌貢獻文章

10 引文 斯高帕斯(Scopus)

摘要

Purpose: Uridine-cytidine kinase (UCK) 2 is a rate-limiting enzyme involved in the salvage pathway of pyrimidine-nucleotide biosyn-thesis. 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 UCK2 gene expression and clinical parameters in patients with breast cancer. Gene set enrichment analysis (GSEA) was performed to identify biological pathways associated with UCK2 gene expression levels. Survival analyses were performed using 10 independent large-scale breast cancer microarray datasets. Results: We found that UCK2 mRNA expression was elevated in breast cancer tissue compared with adjacent nontumorous tissue or breast tissue from healthy controls. High UCK2 levels were correlated with estrogen receptor negativity (p<0.001), advanced tumor grade (p<0.001), and poor tumor differentiation (p<0.001). GSEA revealed that UCK2-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 UCK2 gene expression was associated with poor overall survival in a dose-response manner. The prognostic power of UCK2 was superior to that of TNM staging and comparable to that of multiple gene signatures. Conclusion: These findings suggest that UCK2 may be a promising prognostic biomarker for patients with breast cancer.
原文英語
頁(從 - 到)132-141
頁數10
期刊Journal of Breast Cancer
20
發行號2
DOIs
出版狀態已發佈 - 六月 1 2017

    指紋

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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