Although
orotate phosphoribosyltransferase (OPRT EC 2.4.2.10) is a key
enzyme related to the first-step activation process of
5-fluorouracil, and therefore it has been shown to be an important
enzyme that enables to predict sensitivity to
5-fluorouracil, the clinical and prognostic significance of
protein and/or gene expression of OPRT has not been well established in gastric
carcinoma. We examined the
protein level, and
mRNA expression of OPRT in gastric
carcinoma tissues and relationships with clinicopathologic factors and prognosis were evaluated. A total of 75 surgically-resected gastric
carcinoma tissues were subjected to the study. An enzymelinked
immunosorbent assay (ELISA) was used to accurately assess intratumoral OPRT, and gene expressions of OPRT were examined using a real-time PCR method. Survival of patients with gastric
carcinoma in relation to OPRT
protein levels was analyzed using Kaplan-Meier methods along with log-rank test. The mean value of OPRT was 5.4+/-3.6 ng/mg
protein, and it was significantly higher in patients with differentiated-type and invasive-type gastric
carcinoma. The prognosis of patients in the high OPRT group was better than for those with low OPRT (p<0.05). There was a significant correlation between OPRT levels measured by ELISA and OPRT
mRNA expression (p<0.05). Determination of OPRT levels is a useful tool to predict the
biological characteristics of gastric
carcinoma and possibly predict sensitivity to fluoropyrimidine-based anticancer
chemotherapy,particularly
dihydropyrimidine dehydrogenase-inhibitory fluoropyrimidine, in patients with gastric
carcinoma.