Overexpression of thymidylate synthetase confers an independent prognostic indicator in nasopharyngeal carcinoma

Sung Wei Lee, Tzu Ju Chen, Li Ching Lin, Chien Feng Li, Li Tzong Chen, Chung-Hsi Hsing, Han Ping Hsu, Chia Jung Tsai, Hsuan Ying Huang, Yow Ling Shiue

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25 引文 斯高帕斯(Scopus)

摘要

Data mining on public domain identified that thymidylate synthetase (TYMS) and dihydrofolate reductase (DHFR) transcripts were significantly higher expressed in nasopharyngeal carcinoma (NPC). In the folate pathway, TYMS catalyzes the methylation of deoxyuridylate to deoxythymidylate using 5,10-methylenetetrahydrofolate [5,10-CH2=THF, derived from tetrahydrofolate (THF)], as a cofactor. This function maintains the thymidine-5-prime monophosphate pool critical for DNA replication and repair and, THF is generated from dihydrofolate (DHF) through the activity of DHFR. Immunoexpression of TYMS and DHFR were retrospectively assessed in biopsies of 124 consecutive NPC patients without initial distant metastasis and treated with consistent guidelines. The outcome was correlated with clinicopathological features and patient survivals. Results indicated that high TYMS (50%) expressions were correlated with primary tumor (p=0.008) and AJCC stage (p=0.006), and high DHFR (50%) expression were correlated with nodal status (p=0.039) and AJCC stage (p=0.029) (7th American Joint Committee on Cancer), respectively. In multivariate analyses, high TYMS expression emerged as an independent prognosticator for worse disease-specific survival (p<0.001), distal metastasis-free survival (p=0.002) and local recurrence-free survival (p<0.001), along with AJCC stage. Therefore, TYMS expression is common and associated with adverse prognosticators and might confer tumor aggressiveness through dysregulation of the nucleotide biosynthetic process.

原文英語
頁(從 - 到)83-90
頁數8
期刊Experimental and Molecular Pathology
95
發行號1
DOIs
出版狀態已發佈 - 8月 2013
對外發佈

ASJC Scopus subject areas

  • 病理學與法醫學
  • 分子生物學
  • 臨床生物化學

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