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Prognostic significance of thymidylate synthase in postoperative non-small cell lung cancer patients

Authors Zhao H, Ma G, Zou B, Li M, Lin S, Zhao L, Guo Y, Huang Y, Tian Y, Xie D, Zhang L

Received 28 March 2014

Accepted for publication 30 April 2014

Published 16 July 2014 Volume 2014:7 Pages 1301—1310

DOI https://doi.org/10.2147/OTT.S65067

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4


Hong-Yun Zhao,1,* Guo-Wei Ma,1,* Ben-Yan Zou,1,* Mei Li,1 Su-Xia Lin,1 Li-Ping Zhao,2 Ying Guo,1 Yan Huang,1 Ying Tian,1 Dan Xie,1 Li Zhang1

1Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 2Department of Medical Oncology, Zhongshan Hospital of Sun Yat-Sen University, Zhongshan People’s City Hospital, Zhongshan, People’s Republic of China

*The first three authors contributed equally to this work

Abstract: The aim of the present study was to investigate the clinicopathologic/prognostic significance of thymidylate synthase (TS), orotate phosphoribosyltransferase (OPRT), and thymidine phosphorylase (TP) proteins in postoperative non-small cell lung cancer (NSCLC) patients. Microarray slides from a set of 178 NSCLC patients were used for the detection of TS, OPRT, and TP expression by immunohistochemistry. The correlation between clinicopathologic factors and protein expression of three proteins was analyzed. Ninety seven carcinomas (57.4%) were TS-positive, 90 carcinomas (53.9%) were OPRT-positive, and 102 carcinomas (69.4%) were TP-positive. Compared with the TS-positive patients, the overall survival (OS) was significantly lower in the TS-negative patients (hazard ratio [HR] =1.766, 95% confidence interval [CI] =1.212–2.573, P=0.003). Significant differences between TS-positive and TS-negative patients was also observed in the following stratified analyses: 1) adenocarcinoma subgroup (HR =2.079, 95% CI =1.235–3.500, P=0.006); 2) less than 60-year-old subgroup (HR =1.890, 95% CI =1.061–3.366, P=0.031); 3) stage II/III subgroup (HR =1.594, 95% CI =1.036–2.453, P=0.034); and 4) surgery plus adjuvant therapy subgroup (HR =1.976, 95% CI =1.226–3.185, P=0.005). However, the OS was not significantly correlated with OPRT or TP protein expression. This study demonstrates that the TS level in tumor tissues may be a useful marker to predict the postoperative OS in NSCLC patients.

Keywords: orotate phosphoribosyltransferase, thymidine phosphorylase

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