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

Abstract

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.

Prognostic nomogram for previously untreated patients with esophageal squamous cell carcinoma after esophagectomy followed by adjuvant chemotherapy

“…Third, the prognostic variables we used in this study were rather restricted to common clinicopathological features. In the future, with more and more biological and genetic features (32,(39)(40)(41)(42)(43)(44) become more and more relevant, as well as hematological information such as plasma fibrinogen level (45), platelet count (45) and lymphocyte-monocyte ratio (46), and finally, with the optimization of clinical treatment strategy, sustained refinement of the nomogram is undoubtedly necessary, in which more and different prognostic factors might be included in the model.…”

Retrograde Lymphatic Spread of Esophageal Cancer

“…The mechanisms of the retrograde lymphatic spread of cancer cells in the current case can be explained by the following phenomena: an increase in downstream intralymphatic pressure caused by lymphatic obstruction following cancer invasion or by an extrinsic lymph pump that depends on adjacent tissue movements, such as swallowing, esophageal peristalsis, arteriolar vasomotion, arteriolar pulsation, or respiration 7 ; contractile dysfunction of the lymphatic wall caused by a tumor thrombus or by physiologically active substances, such as VEGF-C, which may have been released by cancer cells or lymphatic endothelial cells 8 , 9 ; and intermittent regurgitation of the lymphatic valve caused by lymphatic ectasia or by the adhesion of cancer cells to lymphatic endothelial cells, presumably via adhesion-related molecules, such as ICAM-1, which have been expressed by either type of cell. 10 , 11 …”

Visfatin upregulates VEGF-C expression and lymphangiogenesis in esophageal cancer by activating MEK1/2-ERK and NF-κB signaling

“…High levels of VEGF-C expression correlate with advanced stage disease, deeply invasive tumors and lymph node metastasis [ 29 ]. Higher levels of VEGF-C expression are linked to lower 5-year survival rates in esophageal squamous cell carcinoma (ESCC) [ 30 , 31 ]. Lymphangiogenic mediators are regulated by various signal transduction pathways in cancer, such as the MEK1/2-ERK and NF-κB pathways [ 32 , 33 ].…”