Expression Of Wnt-5a, β-catenin And E-cadherin In Gastric Carcinoma And Its Clinical Significance

Objective To detect the expression of Wnt-5a mRNA in gastric carcinoma and the corresponding peri-tumor tissue,and the expression of Wnt-5a,β-catenin and E-cadherin protein were also examined in gastric carcinoma(GC),peri-tumor tissue and normal stomach tissue.Approach the relationship between expression of Wnt-5a with the occurrence of GC and clinicopathologic characters,and discuss the correlation with the expression of Wnt-5a,β-catenin and E-cadherin in order to explore the mechanism of molecular biology for the occurrence and development of GC.We therefore wanted to investigate the role of Wnt-5a expression in tumor,with focus on diagnosis and prognosis in GC,Wnt-5a is not only a good prognostic indicator of gastric cancer but also a candidate for a molecular target of therapy for gastric cancer.Methods Real time RT-PCR was performed in ten fresh gastric carcinoma sample and the corresponding normal tissue to detect mRNA expression of Wnt-5a gene. Eighty-four gastric carcinoma cases and the corresponding peri-tumor tissues and twenty normal stomach mucosa were examined Wnt-5a,β-catenin and E-cadherin by SP immunohistochemical method.The results was treated by matched-pairs T test, chi-square test and Spearman Correlation analysis.Results 1.Real time RT-PCR analysis showed that Wnt-5a mRNA was overexpressed in GC, and the level of Wnt-5a mRNA in tumor and normal region were5.919±1.869,1.281±0.744 respectively,with a significant difference(P<0.05).Wnt-5a mRNA was up-regulation in 80%(8/10 cases) GC.2.Wnt-5a protein was negative in all normal gastric tissue,the positive expression rate of Wnt-5a protein in peri-tumor tissue and GC was 14.29%(12/84cases),40.54% (34/84cases) respectively.Wnt-5a protein was positive in 5 cases which develop intestinal metaplasia and 5/8 cases which develop atypical hyperplasia of all the peri-tumor tissue.Compare with the normal tissue,expression of Wnt-5a has a significant highly positive rate in gastric carcinoma(P<0.05),but no significance in peri-tumor tissue(P>0.05);negative expression of Wnt-5a in mucinous adenocarcinoma has a significant difference compare with that in tubular adenocarcinoma,papillary adenocarcinoma and signet-ring cell carcinoma,but no significant difference with histology type in group comparison(P>0.05).Abnormal expression of Wnt-5a was significantly associated with advanced TNM stages (P<0.001),and lymph node metastasis(P<0.01),but no relation with tumor grades(P>0.05).3.The membranous expression rate ofβ-catenin in normal gastric mucosa was 100%. it was observed in cytoplasm and/or cellular nucleus in GC and peri-tumor tissue, and the positive rate were respectively:70.23%(59/84),38.10%(29/84),of the total carcinoma casesβ-catenin cellular nucleus expression was observed in 19.05%(16 cases).Abnormal expression ofβ-catenin has statistical significance (P<0.01) in tumor and peri- tumor tissue compare with normal tissue,and the abnormal expression ofβ-catenin was associated with advanced tumor stages (P<0.05) and lymph node metastasis(P<0.05),but no correlation with tumor grades(P>0.05).4.The membranous expression rate of E-cadherin in normal mucosa was 100%,The low/loss membranous expression rate of E-cadherin in peri-tumor tissue and gastric carcinoma were 57.14%(48/84) and 84.5%(13/84) respectively.Compare with normal tissue,down-regulation of E-cadherin has a significant highly positive rate in gastric carcinoma(P<0.05),but no significance in peri-tumor tissue(P>0.05); Reduced expression of E-cadherin was significantly associated with advanced tumor stages,lymph node metastasis and the tumor grades(P<0.05,respectively).5.The expression of Wnt-5a was correlated withβ-catenin(r=-0.367,P<0.01) and E-cadherin(r=0.262,P<0.05) in GC.Conclusions:1.Wnt-5a mRNA and protein were up-regulation in GC.Wnt-5a may play a tumor stimulator function,and Wnt-5a gene may have been activated in early period of tumorigenesis.The high expression of Wnt-5a may be a frequent event in the occurrence and development of GC,and was associated with advanced tumor stages and lymph node metastasis.Wnt-5a protein may become an useful prognosis indicator of GC.2.β-catenin was detected in cytoplasm and/or cellular nucleus in gastric carcinoma and peri-tumor tissue,which indicate thatβ-catenin may participate in the occurrence of gastric caicinoma.Expression ofβ-catenin was associated with advanced tumor stages and lymph node metastasis.3.Reduced membranous expression of E-cadherin was a significant event in GC and associated with advanced tumor stages,lymph node metastasis and the tumor grades.4.The expression of Wnt-5a was negative correlated withβ-catenin in GC, suggesting that the expression of Wnt-5a andβ-catenin is mutually exclusive.The two molecules may suppress the expression of each other,and may play important role in the occurrence of GC via different signal pathway.5.The expression of Wnt-5a was positively correlated with E-cadherin in GC.Wnt-5a may besides play direct function in the occurrence and progression of GC and also may be in coordination with the expression of E-cadherin to enhance the invasion and metastasis of GC.