Background and purpose: Thymidylate synthetase (TS) and thymidine phosphorylase (TP) are the key enzymes in metabolism of fluorouracil drugs

and related to the chemotherapy response and prognosis in gastric cancer patients receiving fluorouracil-based chemotherapy. This study aimed to investigate the correlations between serum levels of TS

TP and clinical outcome in Chinese patients with advanced gastric cancer receiving fluorouracilbased chemotherapy. Methods: Serum samples prior to chemotherapy were collected from 109 patients receiving first-line fluorouracil-based chemotherapy in Peking University Cancer Hospital from Jan. 2006 to Oct. 2008. TS and TP levels were analyzed using ELISA assay. Results: TS expressions was higher in patients with proximal gastric cancer than those in patients with distal gastric cancer primary (P=0.035)

and TP expression in patients with peritoneal metastasis was significantly lower than those in patients without peritoneal metastasis (P0.001). Patients with high level of TS had higher clinical benefit rate (CBR) than patients with low level of TS (68.75% vs 47.1%

P=0.029)

but no difference was seen between TS levels and survival. The median progression-free survival (PFS) and overall survival (OS) in patients with high level of TP were higher than those in patients with low levels of TP (PFS: 177 d vs 113 d

P=0.018; OS: 399 d vs 234 d

P=0.227). Combined analysis of TS and TP

the results indicated that patients with low TS and high TP levels had significantly longer PFS and OS than patients with low TS and high TP levels (median PFS: 182 d vs 87 d

P=0.042; median OS: 439 d vs 233 d

P=0.019). Cox multivariate regression analysis demonstrated that TP was an independent prognostic factor in patients with low level of TS (HR=1.913

95% CI: 1.107–3.564

P=0.041). Conclusion: In Chinese patients with advanced gastric cancer receiving first-line fluorouracil-based chemotherapy

patients with high level of TS have a better efficacy and patients with high level of TP have a better prognosis. Especially

patients with TS low and TP high level have the longest PFS or OS.