The Basic Research And Clinicopathological Significance Of HIF-1α And VEGF Expression In Esophageal Squamous Carcinoma

Objective:Investigate the expression levels of HIF-1α,VEGF protein and their mRNA in esophageal carcinoma and normal squamous epithelium tissue,Investigate the relationships of the expression levels of HIF-1α,VEGF with clinicopathological features of esophageal squamous cancer.Furtherly,Investigate the relationship of HIF-1αwith VEGF.Methods:42 patients' novel tissues were collected,and HIF-1αand VEGF were examined in esophageal squamous cancer tissue and normal end squamous epithelium tissue with real-time quantitive PCR for gene expression and immunohistochemistry for protein expression.the difference of HIF-1α,VEGF and their mRNAs'expressions between esophageal squamous cancer tissue and normal end squamous epithelium tissue was analyzed;the correlation between VEGF mRNA and HIF-1αmRNA was also analyzed.The pathology results were obtained and were classified into T1-T2 and T3-T4 two groups according to the depth of cancer invasion,Ⅰ,Ⅰ-Ⅱ,ⅡandⅡ-Ⅲ,Ⅲgroups according to cancer tissue differentiation,N0 and N1 groups according to Lymph node metastasis and lymphatic invasion.The differences between two different groups were analyzed respectively,difference between T1,T2 and T3,T4,Ⅰ,Ⅰ-Ⅱ,ⅡandⅡ-Ⅲ,Ⅲ,N0 and N1 respectively.And the KYSE-150 esophageal carcinoma cell was selected for the study of the relationship of HIF-1αand VEGF with siRNA technology.Results:In esophageal squamous cancer tissue the expressions of HIF-1αmRNA,VEGF mRNA were higher than in normal end squamous epithelium tissue(P=0.014 and P=0.010,respectively).HIF-1αand VEGF protein positive rate are 50%and 77% in esophageal squamous cancer tissue,while 14%and 28%in normal esophageal tissue,which is significant in difference(P=0.001 and P=0.000,respectively).In the esophageal squamous cancer tissue HIF-1amRNA and VEGFmRNA have a close correlation(r=0.87),and tended to be correlated with lymph node metastasis(including lymphatic invasion)(P=0.063 and P=0.073,respectively).Finally,differential HIF-1αexpression was also related to lymph node metastasis(P=0.013);as well as tissue differentiaion(P=0.028).In the esophageal carcinoma cell KYSE-150,the expression level of was decreased when the cells was transfected with HIF-1αmRNA-siRNA,and the expression level of VEGF was also decreased(P＜0.05).Conclusion:In esophageal squamous cell carcinoma tissues the expression levels of HIF-1α,VEGF and their mRNAs were higher than in normal end squamous epithelium tissue.And the expression of HIF-1αprotein correlate with the differentiaion and lymphatic metastasis.In KYSE-150 cells,HIF-1αmRNA-siRNA could silence the expression of HIF-1αmRNA,and inhibited the expression of VEGF,which proved that HIF-1αwas the up-stream regulative factor.SoHIF-1αmight serve as a new index of dignosis of esophageal carcinoma and evaluation of malignancy degree,and also a new target of anti-angiogenesis.