The Expression And Significances Of HUR And Vaseular Endothelial Growth Factor-C In Esophageal Squamous Cell Carcinoma

ObjectiveStudy the expression of HuR and VEGF-C in Esophageal Squamous Cell Carcinoma (ESCC), and correlate results with patients'clinicopathological parameters and survival for providing experimental basis to screen new target for the treatment of ESCC, assessing their usefulness as biological markers for determining early ESCC and lymph node metastasis.Methods1. The expression of HuR and VEGF-C in 58 ESCC tissues and 20 control paracancerous normal tissues were detected by immunohistochemistry staining S-P assay. The correlation between the expression of HuR and VEGF-C and the clinicalpathological parameters and the relationship between the expression of HuR and VEGF-C were analyzed.2. The correlation between HuR and VEGF-C expression and patient outcome was determined by Kaplan-Meier method and Cox proportional hazards regression model.3. Serum VEGF-C levels in 58 patients with ESCC and 20 healthy people were measured by ELISA assay, and the relationships between VEGF-C and different clinicopathological factors was analyzed.Results1. In 58 ESCC tissues, positive rate of cytoplasmic HuR, nuclear HuR and VEGF-C were 46.55%(27/58),75.86%(44/58) and 68.97%(40/58), respectively. Compared With positive rate of cytoplasmic HuR, nuclear HuR and VEGF-C in normal Esophagal tissues,0%(0/20),10.00%(2/20)and 15.00%(3/20) respective-ely,the difference had a statistic significance (P<0.01). Both the expression of cytoplasmic HuR protein and VEGF-C protein were positively correlated with lymph node metastasis, depth of tumor invasion and TNM stages (P<0.05). In addition, the expression of cytoplasmic HuR protein was positively correlated with tumor size. However, the expression of nuclear HuR protein was not correlated with any clinicopathological factors.2. There was an obvious positive correlation between the expression of cytoplasmic HuR and VEGF-C (r=0.351, P<0.05).3. The follow-up visit in the patients showed that five-year survival rate was greatly lower in the positive expression of the cytoplasmic HuR group than that in the negative group (P<0.05). Although the positive expression of nuclear HuR group had a lower 5 year survival rate than the negative group, there is no statistic significance. Meanwhile, the positive expression of VEGF-C group had a lower 5 year survival rate than the negative group obviously (P<0.05). The 5 year survival rate in the cytoplasmic HuR and VEGF-C double positive group was lower than the double negative group obviously. In multivariate analysis using the Cox regression model, the independent prognostic parameters for ESCC patients included cytoplasmic HuR express(RR=2.344; 95% Cl,1.140-4.820;P=0.021), VEGF-C express (RR=2.565; 95% Cl,1.087-6.052;P=0.032) and lymph node metastasis (RR=2.233; 95% Cl,1.068-4.668; P=0.033), had no correlation with nuclear HuR express and other clinicopathological characteristics (?>0.05)。4. We found that the serum VEGF-C level in 58 ESCC patients and 20 healthy controls was (643.58±144.56) pg/ml, (542.74±117.55) pg/ml, respectiv-ely,indicated an obvious statistic difference (P<0.01). The concentrations of VEGF-C were statistically significantly different in stage III and stage IV ESCC patients (665.51±141.20) pg/ml and stage I and stageⅡESCC patients (574.66±137.61) pg/ml (P<0.05). ESCC patients with lymph node metastasis had a higher VEGF-C level (685.51±142.52) pg/ml than those without lymph node metastasis (601.65±136.34) pg/ml (P<0.05).Compared with serum VEGF-C concentration (576.01±140.96) pg/m in patients whose depth of tumor invasion did not overpass serous membrane (T1+T2), serum VEGF-C concentration (576.01±140.96) pg/m in patients whose depth of tumor invasion overpassed serous membrane (T3+T4) elevated notably. Above-mentioned results suggested that Serum VEGF-C level in ESCC patients was closely correlated with TNM stage (?<0.05), lymph node metastasis (P<0.05) and depth of tumor invasion (P<0.05). ConclusionBoth the expression of HuR and VEGF-C in ESCC tissues and VEGF-C level in peripheral blood are closely correlated with malignant tumor progress and lymph nodes metastasis.Therefore, they are considered as poor prognosis markers of ESCC, become potential anti-tumor therapeutic targets.