Supplementary Material for: Vascular Endothelial Growth Factor-C Expression as a Biomarker of Poor Prognosis in Esophageal Squamous Cell Carcinoma: A Meta-Analysis

Background: Vascular endothelial growth factor C (VEGF-C) is involved in the development and progression of tumor angio-/lymphangiogenesis. The purpose of this study is to evaluate whether VEGF-C expression is an indicator of aggressiveness and poor prognosis of esophageal squamous cell carcinoma (ESCC). Method: A meta-analysis was conducted to investigate the association between VEGF-C expression with clinicopathological characteristics and survival of ESCC patients. The dataset was defined by searching PubMed, Embase, Google Scholar, and the Cochrane database for appropriate articles published until April 2014. Result: The final analysis was made from 9 studies, including 656 ESCC patients. Positive VEGF-C expression was defined by immunohistochemistry (IHC) or mRNA expression analysis. The results demonstrated that VEGF-C expression was significantly associated with advanced-stage disease (odds ratio (OR) = 2.29, 95% confidence interval (CI) = 1.37-3.84, P = 0.002), deeper tumor invasion, lymph node metastasis, and lymphatic invasion. The 5-year survival of VEGF-C expression-negative patients was found to be better than that of VEGF-C expression-positive patients (OR = 0.35, 95% CI = 0.21-0.58, P < 0.0001). However, there was no significant association between the VEGF-C expression levels and either poorer tumor differentiation or vascular invasion. Conclusion: The results of the meta-analysis strongly indicate that VEGF-C expression could function as a marker for predicting the aggressiveness and prognosis of ESCC.