Expression Levels of Thymidine Phosphorylase (TP) and Dihydropyrimidine Dehydrogenase (DPD) in Patients with Gastrointestinal Cancer

Abstract

Background: Thymidine phosphorylase (TP) is a key enzyme involved in pyrimidine nucleoside metabolism. Dihydropyrimidine dehydrogenase (DPD) is the major catabolic enzyme of 5-fluorouracil (5-FU). These are important enzymes in the pyrimidine salvage pathway and are considered to be key enzymes for determining the prognosis of patients with gastrointestinal cancer. In the present study, TP and DPD were quantified and evaluated in gastric and colorectal cancer. Patients and Methods: In 111 cases of malignancy, including 30 gastric cancers and 81 colorectal cancers, the expression levels of both TP and DPD in fresh-frozen samples from either tumor or adjacent normal tissue were quantified using enzyme-linked immunosorbent assay (ELISA). The relationships between TP or DPD expression levels in tumor tissues or adjacent normal tissues and clinicopathological factors were evaluated. Results: The TP expression levels in gastric or colorectal tumor tissues were found to be significantly higher than those in the adjacent normal tissue. Although the DPD expression levels in gastric tumor tissue were significantly higher than those in adjacent normal tissue, the DPD expression levels in colorectal tumor tissue were nearly identical to those in the adjacent normal tissue. The DPD expression levels in gastric tumor tissues were significantly higher than those in colorectal tumor tissues. The TP expression levels correlated significantly with the DPD expression levels in tumor or adjacent normal tissues. The DPD expression levels in tumor tissues significantly correlated with those in adjacent normal tissue. Conclusion: The difference in DPD expressions between gastric and colorectal cancer tissues may reflect the organ specificity of the carcinomas and a difference in chemotherapeutic sensitivity to 5-FU or its analogs. The correlation between TP and DPD expression levels suggests the existence of a common regulatory pathway.