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Association of thymidylate synthase expression and clinical outcomes of gastric cancer patients treated with fluoropyrimidine-based chemotherapy: a meta-analysis

Authors Gao Y, Cui J, Xi H, Cai A, Shen W, Li J, Zhang K, Wei B, Chen L

Received 18 October 2015

Accepted for publication 26 January 2016

Published 9 March 2016 Volume 2016:9 Pages 1339—1350


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Jia Fan

Peer reviewer comments 5

Editor who approved publication: Professor Daniele Santini

Yunhe Gao,* Jianxin Cui,* Hongqing Xi,* Aizhen Cai, Weisong Shen, Jiyang Li, Kecheng Zhang, Bo Wei, Lin Chen

Department of General Surgery, Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China

*These authors contributed equally to this work

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.
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: thymidylate synthase, gastric cancer, meta-analysis, fluoropyrimidine-based chemotherapy, clinical outcomes

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