Prognostic and predictive significance of thymidylate synthase protein expression in non-small cell lung cancer: A systematic review and meta-analysis

Article type: Research Article

Authors: Liu, Qingyun^{a; 1} | Yu, Zubin^{b; 1} | Xiang, Ying^a | Wu, Na^a | Wu, Long^a | Xu, Bin^a | Wang, Liang^c | Yang, Ping^d | Li, Yafei^{a; *} | Bai, Li^{e; *}

Affiliations: [a] Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, China | [b] Department of Thoracic Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China | [c] Department of Pathology, MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA | [d] Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MI, USA | [e] Department of Respiratory Disease, Xinqiao Hospital, Third Military Medical University, Chongqing, China

Correspondence: [*] Corresponding authors: Yafei Li, Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, NO.30 Gaotanyan Street, Chongqing 400038, China. Tel.: +86 23 68752293; E-mail: [email protected]; Li Bai, Department of Respiratory Disease, Xinqiao Hospital, Third Military Medical University, Xinqiao Main Street, Chongqing 400037, China. Tel.: +86 23 68755281; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Background:It remains controversial whether thymidylate synthase (TS) protein expression is associated with survival for patients with non-small cell lung cancer (NSCLC). Objective:To evaluate prognostic and predictive significance of tumor TS protein level in NSCLC. Methods:Electronic searches were performed for relevant studies in PubMed, EMBASE, Web of Science, and Chinese Biomedical Literature Database. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were pooled for meta-analysis. Subgroup and sensitivity analyses were performed. Publication bias was evaluated by funnel plot and Begg’s test. Results:Twenty-four studies, including 2280 patients, were eligible. This analysis showed that patients with low TS expression had statistically significantly longer OS and PFS than those with high TS (HR=0.51 and HR=0.49, respectively). Based on TS-targeted drug use status, TS expression was significantly associated with OS in pemetrexed (HR=0.42) and 5-Fluorouracil subgroups (HR=0.34), but not in no TS-targeted drug subgroup. There were similar results for PFS analyses. Sensitivity analysis indicated that the results were robust. Begg’s test did not reveal any publication bias. Conclusion:Low TS protein expression is a favorable predictive factor for better OS/PFS in NSCLC patients treated with TS-targeted drugs. Prognostic value of TS protein expression needs further validation.

Keywords: Non-small cell lung cancer, thymidylate synthase, prognosis, predictive factor

DOI: 10.3233/CBM-140432

Journal: Cancer Biomarkers, vol. 15, no. 1, pp. 65-78, 2015