title: Prognostic impact of elevation of vascular endothelial growth factor family expression in patients with non-small cell lung cancer: an updated meta-analysis.
abstract: BACKGROUND
  The vascular endothelial growth factor family has been implicated in tumorigenesis and metastasis. The prognostic value of each vascular endothelial growth factor family member, particular VEGF/ VEGFR co-expression, in patients with non-small lung cancer remains controversial.
  
  
  METHODS
  Relevant literature was identified by searching PubMed, EMBASE and Web of Science. Studies evaluating expression of VEGFs and/or VEGFRs by immunohistochemistry or ELISA in lung cancer tissue were eligible for inclusion. Hazard ratios (HRs) and 95% confidence intervals (CIs) from individual study were pooled by using a fixed- or random-effect model, heterogeneity and publication bias analyses were also performed.
  
  
  RESULTS
  74 studies covering 7,631 patients were included in the meta-analysis. Regarding pro-angiogenesis factors, the expression of VEGFA (HR=1.633, 95%CI: 1.490-1.791) and VEGFR1 (HR=1.924, 95%CI: 1.220-3.034) was associated separately with poor survival. Especially, VEGFA over-expression was an independent prognostic factor in adenocarcinoma (ADC) (HR=1.775, 95%CI: 1.384-2.275) and SCC (HR=2.919, 95%CI: 2.060-4.137). Co-expression of VEGFA/VEGFR2 (HR=2.011, 95%CI: 1.405-2.876) was also significantly associated with worse survival. For lymphangiogenesis factors, the expression of VEGFC (HR=1.611, 95%CI: 1.407-1.844) predicted a poor prognosis. Co-expression of VEGFC/VEGFR3 (HR=2.436, 95%CI: 1.468-4.043) emerged as a preferable prognostic marker.
  
  
  CONCLUSIONS
  The expression of VEGFA (particularly in SCC and early stage NSCLC), VEGFC, VEGFR1 indicates separately an unfavorable prognosis in patients with NSCLC. Co-expression VEGFA/ VEGFR2 is comparable with VEGFC/VEGFR3, both featuring sufficient discrimination value as preferable as prognostic biologic markers.
authors.affiliation: Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, China E-mail : dujiajun@sdu.edu.cn.
authors.forename: Chun-Long
authors.initials: CL
authors.lastname: Zheng
authors.forename: Chen
authors.initials: C
authors.lastname: Qiu
authors.forename: Mei-Xiao
authors.initials: MX
authors.lastname: Shen
authors.forename: Xiao
authors.initials: X
authors.lastname: Qu
authors.forename: Tie-Hong
authors.initials: TH
authors.lastname: Zhang
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Zhang
authors.forename: Jia-Jun
authors.initials: JJ
authors.lastname: Du
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D042583:Lymphangiogenesis / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000235:genetics; D011379:Prognosis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000096:biosynthesis / Q000378:metabolism*; D016896:Treatment Outcome; D042442:Vascular Endothelial Growth Factors / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D042442:Vascular Endothelial Growth Factors; D040262:Receptors, Vascular Endothelial Growth Factor