Vascular endothelial growth factor C (VEGF-C) in esophageal cancer correlates with lymph node metastasis and poor patient prognosis

Abstract

BackgroundThe diagnosis of lymph node metastasis in esophageal cancer by the presence and number of metastatic lymph nodes is an extremely important prognostic factor. In addition, the indication of non-surgical therapy is gaining more attention. Vascular endothelial growth factor C (VEGF-C) is potentially lymphangiogenic and selectively induces hyperplasia of the lymphatic vasculature. In this study, we investigated the expression of VEGF-C and whether it correlated with various clinico-pathologic findings.MethodsKYSE series of esophageal cancer cell lines and 106 patients with primary esophageal squamous cell carcinomas who had undergone radical esophagectomy were analyzed. VEGF-C mRNA expression was determined by quantitative RT-PCR.ResultsHigh expression of VEGF-C was detected in most of the KYSE cell lines, especially KYSE410, yet, in an esophageal normal epithelium cell line, Het-1A, VEGF-C was not detected. In the clinical specimen, the expression of VEGF-C in the cancerous tissue was higher than in the corresponding noncancerous esophageal mucosa (p = 0.026). The expression of VEGF-C was found to be higher in Stage2B-4A tumors than in Stage0-2A tumors (p = 0.049). When the patients were divided into two groups according to their expression levels of VEGF-C (a group of 53 cases with high expression and a group of 53 cases with low expression), the patients with high VEGF-C expression had significantly shorter survival after surgery than the patients with low expression (p = 0.0065). Although univariate analysis showed that high expression of VEGF-C was a statistically significant prognostic factor, this was not shown in multivariate analysis. In the subgroup of patients with Tis and T1 tumors, the expression of VEGF-C was higher in N1 tumors than in N0 tumors (p = 0.029). The survival rate of patients from the high expression group (n = 10) was lower than that in the low expression group (n = 11), and all the patients in the low VEGF-C expression group survived.ConclusionsThe expression of VEGF-C correlates with lymph node metastasis and poor prognosis. In patients with Tis and T1 esophageal tumors, the expression of VEGF-C may be a good diagnostic factor for determining metastasis of the lymph node.

Clinical implications of PTEN and VEGF expression status, as well as microvessel density in esophageal squamous cell carcinoma

“…VEGF-C is lymphangiogenic, and is able to selectively induce hyperplasia of the lymphatic vasculature. VEGF-C expression is correlated with lymph node metastasis and poor prognosis in esophageal cancer (17)(18)(19). Furthermore, in patients with esophageal tumors, the expression of VEGF-C has been shown to be an effective diagnostic factor for determining metastasis of lymph nodes (17)(18)(19).…”

“…VEGF-C expression is correlated with lymph node metastasis and poor prognosis in esophageal cancer (17)(18)(19). Furthermore, in patients with esophageal tumors, the expression of VEGF-C has been shown to be an effective diagnostic factor for determining metastasis of lymph nodes (17)(18)(19). In a meta-analysis, elevated VEGF expression was shown to be associated with poor survival in patients with esophageal cancer (20).…”

microRNA and inflammatory gene expression as prognostic marker for overall survival in esophageal squamous cell carcinoma

“…Among the 25 inflammatory genes, CYR61, CTGF, VEGF, MCP1, MIF, TGFA and TGFB were selected based on the reports linking their expression to ESCC tumoriogenesis and prognosis. [22][23][24][25][26] The rest of the inflammatory genes were selected from our previous studies on liver, lung and esophageal adenocarcinoma. 9,16,18 We have previously used expression patterns of inflammation-related genes to develop prognostic classifiers for esophageal adenocarcinoma.…”

RNAi-induced K-Ras Gene Silencing Suppresses Growth of EC9706 Cells and Enhances Chemotherapy Sensitivity of Esophageal Cancer

“…Esophageal cancer is one of the most common malignant tumors, with mortality accounting for about a quarter of that of all malignant tumors (Tanaka et al, 2010). At present, surgery and chemoradiotherapy are the two major treatments for esophageal cancer.…”

“…This had been confirmed before our research (Wang et al, 2011). Mutation of K-Ras gene is closely related to carcinogenesis (Tanaka et al, 2010). A lot of researches on the association of K-Ras gene expression with esophageal cancer had been carried out in esophageal cancer tissues and cells in in vitro and animal experiments.…”