Prognostic value of 5-fluorouracil metabolic enzyme genes in Dukes' stage B and C colorectal cancer patients treated with oral 5-fluorouracil-based adjuvant chemotherapy

Abstract

5-Fluorouracil (5-FU) is the most commonly used anticancer drug for colorectal cancer (CRC). In this study, we aimed to clarify the prognostic value of the expression of the 5-FU metabolic enzyme genes, including orptate phosphoribosyl transferase (OPRT), dihydropyrimidine dehydrogenase (DPD), thymidylate synthetase (TS) and thymidylate phosphorylate (TP) genes in CRC patients treated with oral 5-FU-based adjuvant chemotherapy. We examined 103 CRC patients with Dukes stage B and C who underwent oral 5-FU-based adjuvant chemotherapy. Formalin-fixed, paraffin-embedded tumor specimens from primary CRC tissues were dissected by laser-captured microdissection and quantification of mRNA levels of OPRT, DPD, TS and TP were measured by real-time reverse transcription (RT) PCR. The relationship between these 5-FU metabolic enzyme gene levels and disease-free and overall survival rates were examined. The disease-free and overall survival curves of the OPRT mRNA high-expression group were significantly longer than that of the OPRT mRNA low-expression group. The disease-free and overall survival curves of the DPD mRNA high-expression group were significantly shorter than that of the DPD mRNA low-expression group. In contrast, there were no significant differences between the TS or TP mRNA high-expression and low-expression groups in the disease-free and overall survival curves. In a multivariate Cox regression analysis, it was demonstrated that the OPRT mRNA level is an independent prognostic variable for disease-free and overall survival. These results suggest that the OPRT mRNA is a useful indicator in the prediction of disease-free and overall survival in Dukes' B and C stage CRC patients treated with oral 5-FU-based adjuvant chemotherapy.