Expression Levels of Thymidylate Synthase, Dihydropyrimidine Dehydrogenase, and Thymidine Phosphorylase in Patients with Colorectal Cancer

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. In patients with colorectal cancer, 5-fluorouracil-based chemotherapy has been the mainstay of treatment. Many studies have examined whether enzymes involved in 5-fluorouracil metabolism, can be used to predict outcome or sensitivity of cancer cells to 5-fluorouracil-based chemotherapy. We believe that the identification of prognostic factors for outcome, sensitivity to 5-fluorouracil derivatives, and sensitivity to concomitant therapy in patients with colorectal cancer is essential for establishing safer and more effective regimens for chemotherapy or adjuvant chemotherapy that are optimally suited to individual patients with advanced or recurrent