Expression levels of thymidylate synthase, dihydropyrimidine dehydrogenase, and thymidine phosphorylase in patients with colorectal cancer

Anticancer Res. 2012 May;32(5):1757-62.

Abstract

Background: Predictors of the response of colorectal cancer to chemotherapy remain poorly understood. We analyzed the mRNA expression levels of enzymes related to sensitivity to 5-fluorouracil derivatives in patients with colorectal cancer.

Patients and methods: Danenberg tumor profile method (DTP) was used in order to measure mRNA expression levels of thymidylate synthase (TYMS), dihydropyrimidine dehydrogenase (DPYD), and thymidine phosphorylase (TYMP) from 180 patients with colorectal cancer. The relations of expression levels with clinicopathological factors and outcomes were studied.

Results: Higher TYMS expression was associated with greater age, DPYD expression with greater age, poorer differentiation and low invasion, and TYMP expression with poorer differentiation and lack of peritoneal metastasis. DPYD expression positively correlated with TYMP expression. In patients with stage IV disease, high DPYD or TYMP expression was associated with poor outcomes.

Conclusion: mRNA expression of TYMS, DPYD, and TYMP is associated with distinct characteristics and may be useful for predicting survival in patients with stage IV colorectal cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / enzymology*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Dihydrouracil Dehydrogenase (NADP) / genetics*
  • Female
  • Fluorouracil / therapeutic use
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • RNA, Messenger / analysis
  • Thymidine Phosphorylase / genetics*
  • Thymidylate Synthase / genetics*

Substances

  • RNA, Messenger
  • Dihydrouracil Dehydrogenase (NADP)
  • Thymidylate Synthase
  • TYMP protein, human
  • Thymidine Phosphorylase
  • Fluorouracil