Gene expressions for thymidylate synthase (TS), orotate phosphoribosyltransferase (OPRT), and thymidine phosphorylase (TP), not dihydropyrimidine dehydrogenase (DPD), influence outcome of patients (pts) treated with S-1 for gastric cancer (GC)

Abstract

4050 Background: We have reported that patients with low TS, low DPD, high OPRT or low TP tumor showed a high response rate and a long survival time than patients when treated with UFT/LV for colorectal cancer (Clin Cancer Res, 2003, Br J Cancer, 2003). We investigated the association between gene expressions of 5-FU metabolism-relating enzymes (TS, DPD, OPRT, TP) and clinical efficacy in pts of GC treated with S-1. Methods: The study population consisted of all 41 pts with metastatic GC who received the chemotherapy for metastatic disease after resection of primary tumors at Saitama Medical School. S-1 (40 mg/m2) was administrated orally twice a day for consecutive 28 days every 6 weeks. Gene expressions in primary gastric tumors were analyzed by a real-time RT-PCR method. Results: There was no difference in DPD gene expression between responding and non-responding tumors. Responded tumors had lower TS, higher OPRT, or lower TP gene expressions than non-responded tumors. The median values of each gene we...