title: Prognostic and predictive significance of thymidylate synthase protein expression in non-small cell lung cancer: a systematic review and meta-analysis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, China.
authors.forename: Qingyun
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Zubin
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, China.
authors.forename: Na
authors.initials: N
authors.lastname: Wu
authors.affiliation: Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, China.
authors.forename: Long
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Pathology, MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MI, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, China.
authors.forename: Yafei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Respiratory Disease, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Bai
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000473:pathology; D018572:Disease-Free Survival; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis; D013940:Thymidylate Synthase / Q000378:metabolism*
chemical_list: D013940:Thymidylate Synthase
keywords: Non-small cell lung cancer; predictive factor; prognosis; thymidylate synthase