Prognostic Value of Vascular Endothelial Growth Factor Expression in Patients with Esophageal Cancer: A Systematic Review and Meta-analysis

Background: VEGF is a prime mediator of tumorigenesis and metastasis. Various studies assessing the prognostic value of VEGF in patients with esophageal cancer remain controversial. This study aims to comprehensively and quantitatively summarize the evidence on the suitability of VEGF to predict patients' survival. Methods: Searches were applied to PubMed and EMBASE until December 31, 2011, without language restrictions. Studies were assessed for quality using REMARK (Reporting recommendations for tumor MARKer prognostic studies). Data were collected comparing overall survival in patients with high VEGF level with those with low level. We conducted a systematic review of 31 studies (n = 2,387 patients) and completed a meta-analysis of 30 studies (n = 2,345 patients) that correlated VEGF levels with overall survival. Data were synthesized with HRs. Results: The estimated risk of death was 1.82-fold greater in patients with high VEGF expression [95% confidence interval (CI), 1.58-2.08]. The heterogeneity was not significant (P = 0.130) between studies. High VEGF expression was associated with worse survival in esophageal squamous cell carcinoma (HR, 1.81; 95% CI, 1.57-2.10) and there was no significance in between-study heterogeneity (P = 0.185). Data collected were not sufficient to determine the prognostic value of VEGF in patients with esophageal adenocarcinoma. Conclusions: In this meta-analysis, elevated VEGF expression was associated with poor survival in patients with esophageal cancer but not esophageal adenocarcinoma. Impact: These results support further investigation of VEGF expression for predicting poor survival in patients with esophageal carcinoma and may have implications for treatments directed at inhibiting VEGF-mediated angiogenesis. Cancer Epidemiol Biomarkers Prev; 21(7); 1126-34. (C)2012 AACR.