Activation Of Wnt Signaling Pathway And The Abnormal Expression Of The E-cadherin/catenins Related With Gastric Carcinoma

Objective: Gastric carcinoma was one of the malignant digestive tumors whose morbidity and mortality take the lead in our country. Further research about the mechanism of Gastric carcinoma needed to be done to improve the effect of treatment. The object of the study was to evaluate the expression of Wnt2,β-catenin, E-cadherin andα-catenin in gastric cancer, which refer to the Wnt signaling pathway and the E-cadherin/catenins in order to investigate the relationship between them as well as their roles in gastric cancer. It may contribute to the knowledge about the roles these proteins play in gastric carcinoma genesis, development and metastasis, also their association between each other. It can provide valuable molecule index to clinical diagnoses and prognoses.Methods: 1 The expression of Wnt2,β-catenin, E-cadherin andα-catenin were detected by IHC in 62 cases of gastric carcinoma, 35 cases of adjacent carcinoma and 22 cases of normal gastric mucosa.2 The expression of Wnt2,β-catenin were detected by FCM in 35 cases of gastric carcinoma, 15 cases of adjacent carcinoma and 15 cases of gastric mucosa. 3 SPSS 11.5 was applied to analyze the results of experiment.Results: 1 The expression ofβ-catenin in cell membrane decreased and conversely the expression ofβ-catenin in cytoplasm increased from normal gastric mucosa to gastric carcinoma, and there was statistical significance between 3 groups (P<0.01); The weak expression ofβ-catenin in cell membrane and the strong expression ofβ-catenin in cytoplasm were correlated with invasion depth, lymphatic metastasis, clinical stage, but not with pathology classification, age and sex. The expression ofβ-catenin was also detected by FCM. The flurescent index of gastric carcinoma, adjacent carcinoma and normal gastric mucosa were 1.00±0.06, 0.97±0.05and 0.88±0.07. There was statistical significance between 3 groups (P<0.01).2 The expression of Wnt2 was obviously stronger in carcinoma than that in adjacent carcinoma and normal gastric mucosa(P<0.01); The abnormal expression of Wnt2 was correlated with invasion depth, lymphatic metastasis, clinical stage, but not with pathology classification, age and sex. The expression of Wnt2 was also detected by FCM. The flurescent index of gastric carcinoma, adjacent carcinoma and normal gastric mucosa were 1.00±0.11, 1.08±0.65 and 4.95±1.54. There was statistical significance between 3 groups (P<0.01).3 The abnormal rate of the expression of E-cadherin in carcinoma group was obviously higher than that in adjacent carcinoma group and normal mucosa group(P<0.01). The abnormal expression of E-cadherin was correlated with invasion depth, lymphatic metastasis, pathology classification, clinical stage, but not with age and sex.4 The expression ofα-catenin decreased from normal gastric mucosa to gastric carcinoma(P<0.01); The abnormal expression ofα-catenin only was correlated with pathology classification, but not with invasion depth , lymphatic metastasis, clinical stage, age and sex.5 The Spearman rank correlation analysis method was used to analyze the correlation of Wnt2,β-catenin, E-cadherin andα-catenin. It showed that the expression of Wnt2 was positively related to that ofβ-catenin in cytoplasm (P<0.01), but has no correlation with the expression ofβ-catenin in cell membrane,α-catenin and E-cadherin, however, it might show negative tendency(exceptα-catenin); The expression of E-cadherin was negatively related to that ofβ-catenin in cytoplasm(P<0.01), and posotively related to the expression ofβ-catenin in cell membrane andα-catenin(P<0.01); The expression ofα-catenin was positively related to that ofβ-catenin in cell membrane (P<0.01),and negatively related toβ-catenin in cytoplasm expression (P<0.01).Conclusions: 1 The expression of Wnt signaling pathway's signal protein Wnt2 in carcinoma group was obviously higher than that in adjacent carcinoma group and normal mucosa group. The expression ofβ-catenin in cell membrane was weaker and the expression ofβ-catenin in cytoplasm was stronger in carcinoma group than that in adjacent carcinoma group and normal mucosa group. It indicated that this signaling pathway was involved in tumorigenesis.2 The expression of Wnt2 was positively related to that ofβ-catenin in cytoplasm, indicating that the up-regulation expression of Wnt2 might be one of the reasons to induce the abnormal accumulations ofβ-catenin in cytoplasm. There was an obvious relationship between the abnormal expression ofβ-catenin and invasion depth, lymphatic metastasis, clinical stage, indicating that the abnormal expression ofβ-catenin was significantly related with invasion and metastasis of gastric carcinoma.3 The expression of E-cadherin in carcinoma group was obviously lower than that in adjacent carcinoma group and normal mucosa group. It indicated that E-cadherin was involved in tumorigenesis. The abnormal expression of E-cadherin was correlated with invasion depth, lymphatic metastasis, pathology classification, clinical stage, indicating that it might play an important role in invasion and metastasis of gastric carcinoma.4 The expression ofα-catenin in carcinoma group was obviously lower than that in adjacent carcinoma group and normal mucosa group. It indicated thatα-catenin was involved in tumorigenesis. The abnormal expression ofα-catenin was not correlated with invasion depth, lymphatic metastasis, pathology classification, clinical stage.5 Besides participating cell adhesion, E-cadherin might interact with Wnt signaling pathway. It had effect on the invasion and metastasis of gastric carcinoma through changing the intracellular distribution ofβ-catenin.