Prognostic impact of orotate phosphoribosyl transferase (OPRT) activity in resectable colorectal cancers (CRC) treated by 5-FU-based adjuvant chemotherapy

Abstract

3574 Background: Dihydropyrimidine dehydrogenase and thymidylate synthase are 5-FU metabolism and target enzyme, and has been studied as prognostic factors in CRC. Meanwhile, phosphoribosylation of 5-FU is an essential step leads to tumor growth inhibition and OPRT is the main enzyme that involves in this conversion of 5-FU to FUMP. The aim of this study was to evaluate the prognostic relevance of OPRT activity in CRC patients treated by 5-FU-based adjuvant chemotherapy. Methods: Surgical specimen was obtained from resectable CRC patients who were subsequently treated by 5-FU-based adjuvant chemotherapy. OPRT activity in the extract of tumor tissue was determined by the method of Laskin et al. Disease-free survival (DFS) and overall survival (OS) were calculated using Kaplan-Meier estimate. Results:During 1999 to 2003, tumor tissue was collected from 124 CRC patients and then the patients were followed for 3.7 years (Median). Patients were divided into 2 groups by the cut-off value of tumor OPRT (0.147 nmol/min/mg protein) determined by maximal χ2 method (high group (≥0.147): n=102, low group (<0.147): n=22). There were no significant imbalances in T and N value between 2 groups. 5-year DFS for high and low group were 75.7% and 56.9% (p=0.05, log-rank test) and OS were 84.6% and 58.4% (p=0.01), respectively. Conclusions: Lower OPRT activity in tumor tissue was associated with poor survival in resectable CRC patients treated by 5-FU-based adjuvant chemotherapy and this research clarified that OPRT assay is indispensable for the determination of 5-FU-based adjuvant chemotherapy indication. Thus, the application of OPRT assay to routine clinical practice should be considered prior to 5-FU-based adjuvant chemotherapy. No significant financial relationships to disclose.