Clinical and prognostic significance of protein and gene expression of orotate phosphoribosyltransferase in gastric carcinoma

摘要

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.