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 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.

背景：血管内皮生长因子C（Vascular endothelial growth factor C，VEGF-C）参与肿瘤血管生成与淋巴管生成的发生及进展过程。本研究旨在评估VEGF-C表达是否可作为食管鳞状细胞癌（esophageal squamous cell carcinoma，ESCC）侵袭性与不良预后的标志物。方法：本研究采用荟萃分析方法，探究VEGF-C表达与食管鳞状细胞癌患者的临床病理特征及生存结局的关联。本数据集通过检索PubMed、Embase、Google Scholar及Cochrane数据库，筛选截至2014年4月发表的符合标准的相关文献而构建。结果：最终纳入9项研究，共包含656例食管鳞状细胞癌患者用于本次分析。VEGF-C阳性表达通过免疫组化（immunohistochemistry，IHC）或mRNA表达分析进行判定。结果显示，VEGF-C表达与疾病晚期（比值比（odds ratio，OR）=2.29，95%置信区间（confidence interval，CI）=1.37~3.84，P=0.002）、更深的肿瘤浸润深度、淋巴结转移及淋巴管侵犯显著相关。VEGF-C表达阴性患者的5年生存率显著高于阳性患者（OR=0.35，95%CI=0.21~0.58，P结论：本荟萃分析结果强烈表明，VEGF-C表达可作为预测食管鳞状细胞癌侵袭性与预后的标志物。