Predictive Value of Thymidylate Synthase Expression in Gastric Cancer: A Systematic Review with Meta-analysis

Purpose: The relationship between thymidylate synthase (TS) expression and outcomes in gastric cancer(GC) patients remains controversial, although most studies reported poor survival and reduced response tofluoropyrimidine were related to high TS in tumors. We carried out a systematic review of the literature withmeta-analysis to estimate the predictive value of TS expression from published studies.
Methods: We indentified24 studies analysing the outcome data in gastric cancer stratified by TS expression. Effect measures of outcomewere hazard ratios (HRs) for overall survival (OS) and event-free survival (EFS), or the odds ratio (OR) foroverall response rate (ORR). HRs and ORs from these eligible studies were pooled using random-effects metaanalysis.
Results: Fifteen studies investigated outcomes in a total of 844 patients with advanced GC, and ninestudies investigated outcomes in a total of 1,235 patients with localized GC undergoing adjuvant therapy. Metaanalysisof estimates showed high TS expression was significantly associated with poor OS in the advanced setting(HR: 1.43, 95%CI: 1.08 - 1.90), and poor EFS in the adjuvant setting (HR: 1.53, 95%CI: 1.01 - 2.32). Subgroupanalysis demonstrated TS expression to haves even greater value in predicting OS, EFS and ORR in advancedGC patients treated with fluoropyrimidine monotherapy (HR for OS: 2.32, 95%CI: 1.53 - 3.50; HR for EFS:1.76, 95%CI: 1.19 - 2.60; OR for ORR: 0.32, 95%CI: 0.11 - 0.95).
Conclusion: High levels of TS expression wereasssociated with a poorer OS for advanced GC patients compared with low levels. In the adjuvant setting, highTS expression was also associated with a worse EFS. Additional studies with consistent methodology are neededto define the precise predictive value of TS.