Open Access Highly Accessed Open Badges Research article

The pemetrexed-containing treatments in the non-small cell lung cancer, is -/low thymidylate synthase expression better than +/high thymidylate synthase expression: a meta-analysis

Lei Wang12, Rui Wang12, Yunjian Pan12, Yihua Sun12, Jie Zhang12* and Haiquan Chen12*

Author Affiliations

1 Department of Thoracic Surgery, Shanghai Medical College, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai 200032, China

2 Department of Oncology, Shanghai Medical College, Fudan University Shanghai Cancer Center, Shanghai, China

For all author emails, please log on.

BMC Cancer 2014, 14:205  doi:10.1186/1471-2407-14-205

Published: 19 March 2014



The predictive value of thymidylate synthase (TS) for clinical sensitivity to pemetrexed-containing chemotherapy in patients with non-small cell lung cancer (NSCLC) remains controversial. This meta-analysis is performed to provide an assessment of whether expression variations of TS are associated with objective response in patients with NSCLC treated with pemetrexed-containing chemotherapy.


An electronic search was conducted using the databases MEDLINE, EMBASE and CNKI, from inception to June 10th, 2013. A systemic review of the studies on the association between TS expression in NSCLC and objective response of pemetrexed-containing regimen was performed. Pooled odds ratios (OR) for the response rate were calculated using the software Revman 5.0.


There were a total of 526 patients in the eight studies that met our criteria for evaluation. +/high expression of TS was found in 269 patients (51.1%), and -/low expression for this gene was found in 257 (48.9%) patients. The objective response rate for pemetrexed-containing chemotherapy was significantly higher in patients with -/low expression TS expression (OR = 0.45; 95% CI, 0.29–0.70; p = 0.0004). Although patients with -/low expression of TS have a longer median overall survival time and progression free survival time than those with +/high expression of TS, the difference was not statistically significant.


/low expression of TS was associated with higher objective response in NSCLC patients treated with pemetrexed-containing chemotherapy. TS may be a suitable marker of sensitivity to pemetrexed-based chemotherapy in patients with NSCLC.

Thymidylate synthase; Pemetrexed; Lung cancer; Meta-analysis