The Expression Of DLL4and VEGF In Patients With Esophageal Squamous Cell Carcinoma And The Relationship With MVD In Tumor

Objective:Angiogenesis depends on the interaction of a variety of promoting factors and inhibiting factors,Delta-like ligand4(DLL4)is one of the Notch familiy ligands that is upregulated by Vascular cndothelial growth factor(VEGF) and is reported to have a role in tumor angiogenesis. Blocking DLL4selectlly Can inhibit tumor growthin animal models, Evidence from xenograft studies suggest that inhibiting DLL4-Notch signaling pathway may overcome resistance to anti-VEGFtherapy,combination therapy show better. Therefore, DLL4is expected to become a new target for anti—angiogenic, therapy. The aim of this study was to measure the expression of DLL4, VEGF and calculate the microvessel density(MVD), determined using CD34labeled Vascular endothelial cell in Esophageal Squamous Cell Carcinoma tissues and adjacent tissues; analyze their relationships with angiogenesis of Esophageal Squamous Cell Carcinoma tissues and determine if protein expression correlated with patients,clinicopathological parameters,including gender,age, tumor diameter, The degree of local infiltrati on,clinicalstage,histological grade,lymph node metastasis.Methods:1. Collected seventy-one specimens of surgically resected and paraffin-embedded human Esophageal Squamous Cell Carcinoma tissues andtheir adjacent tissues as comparison2.The expression of DLL4and VEGF、CD34protein in Esophageal Squamous Cell Carcinoma tissues and adjacent tissues were determined by immunohistochemistry.3. Statistical analysis:The data was analy zed by SPSS17.0, Ttest,Pearson Chi-square and Spearman,s rank correlation analysis were performed.A probability(P)-value less than0.05was considered statistically significant.Results:1. In Esophageal Squamous Cell Carcinoma tissues, DLL4and VEGF protein stained as brown granules, mainly con centrated in the cytoplasm, the membrane also had a small amount of expression, the expression of DLL4、VEGF、MVDvalue in Esophageal Squamous Cell Carcinoma tissues and adjacent tissues is significant variation(DLL4χ2=58.197, P<0.001, VEGFx2=54.192, P<0.001, MVDt=19.997, P<0.001), have statistical significance.2.The protein have no relation with patients’gender (DLL4χ2=0.318, P=0.573, VEGFχ2=1.452, P=0.228, MVDt=1.832, P=0.054),age(DLL4χ2=1.347, P=0.246, VEGFχ2=0.114, P=0.736, MVDt=-0.639, P=0.525), The expression of DLL4and VEGF、MVD Was closely related with tumor diameter (DLL4χ2=5.071, P=0.024, VEGFχ2=8.63, P＝0.003, MVDt=-5.091, P<0.001), The degree of local infiltration (DLL4χ2=6.015, P=0.013, VEGFx2=23.213, P<0.001, MVDt=-5.733, P<0.001) clinical stage(DLL4χ2=7.292, P=0.007, VEGFx2=3.889, P=0.049, MVD t=-4.998, P<0.001), histological grade (DLL4χ2=11.511, P=0.001, VEGFx2=7.445, P=0.006, MVDt=-2.013, P=0.049) and lymph node metastasis(DLL4χ2=10.789, P=0.001, VEGFχ2=4.559, P=0.033, MVDt=-4.325, P<0.001).3.MVDvalue in cases with both DLL4and VEGF-positive group was higher compared to the both of them negative and only one of them positive group (t=6.316, P<0.0001),Under the spearman correlation analysis,there was significant positive correlation between DLL4expression and VEGF and MVD value (rs=0.545, P<0.001, rs=0.594, P<0.001),and so do VEGF expression and MVDvalue in Esophageal Squamous Cell Carcinoma tissues (rs=0.508, P<0.001)Conclusion:1. DLL4and VEGF protein and MVDexpression in Esophageal Squamous Cell Carcinoma tissues significantly higherthan adjacent tissues, high expression may indicate a poor prognosis.2.Expressions of DLL4andVEGF protein,MVDvalue in Esophageal Squamous Cell Carcinoma tissues show a significant correlation with tumordiameter,the degree of local infiltration clinicalstage, histologicalgrade and lymphnode metastasis, which suggest thattheir expressions are closely related t0invasion and metastasis of Esophageal Squamous Cell Carcinoma. The higher value of MVDin Esophageal Squamous Cell Carcinoma is updated with DLL4, VEGF richer expression, which indicate that the both of them may have some function in the form of micro Vascular angiogenesis in Esophageal Squamous Cell Carcinoma.3. There exists a positive correlation between DLL4and VEGF, and both of them correlate positively with MVD, which suggest that vEGF may be an important factor in inducing the up-regulation of DLL4,and both of them may have a synergistic effect in invasion,metastasis and angiogenesis of Esophageal Squamous Cell Carcinoma tissues.4.DLL4is expected to become a new target for cancer therapy.