Purpose: Although several studies have suggested an association between thymidylate synthase (TS) expression and outcomes of gastric cancer (GC) patients treated with fluoropyrimidine-based chemotherapy (FUC), the predictive value of TS for response and survival in this setting is unclear. This meta-analysis aimed to estimate prognostic and predictive significance of TS more precisely.
Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science databases for literature published up to June 2015. Primary outcomes included hazard ratios (HRs) for overall survival (OS), and event-free survival (EFS) and odds ratio (OR) for chemotherapy response. Fixed- or random-effects models were used to calculate pooled HR and OR according to heterogeneity.
Results: A total of 2,442 GC patients in 25 studies met our inclusion criteria. Response rates for FUC were significantly lower in patients with high TS expression than in those with low expression (OR: 0.43, 95% confidence interval [CI]: 0.22-0.84, P=0.013). High TS expression was significantly correlated with unfavorable OS (HR: 1.62, 95% CI: 1.28-2.05, P<0.001) and EFS (HR: 1.54, 95% CI: 1.22-1.93, P<0.001) in advanced disease. However, TS expression was not significantly related to OS (HR: 1.06, 95% CI: 0.74-1.50, P=0.760) or EFS (HR: 1.16, 95% CI: 0.84-1.61, P=0.374) in the adjuvant setting.
Conclusion: Higher TS expression might predict drug resistance and adverse prognosis in patients with advanced GC treated with FUC.
Keywords: clinical outcomes; fluoropyrimidine-based chemotherapy; gastric cancer; meta-analysis; thymidylate synthase.