The Relationship Between The Methylation Status Of E-cadherin And β-catenin Expression In Renal Cell Carcinoma

Objective: Renal cell carcinoma is the majority of malignant tumor.It has a increasing tendency recently, but the moleular mechanisms of developmen has not been well known. Most of the renal cell carcinoma patients are presented with advanced disease because early stage renal cell carcinoma does not have apparent symptoms. It's necessary to research its pathogenesis in order to decrease the incidence and mortality of renal cell carcinoma, so as to offer reliable biomarkers and methods for early prevention, diagnosis and therapy.The object of the study regard renal cell carcinoma as study object now, In this research E-cadherin gene methylation and its revelant expressions of theβ-catenin is detceted in renal cell carcinoma and non-cancerous renal tissue, to explore their role in the process of tumorigenesis, progression, invasion and metastasis of renal cell carcinoma and their correlation, to provide new theory and experiment evidence for pathogenesy, gene therapy and immunotherapy. It may contribute to the knowledge about the roles these proteins play in renal carcinoma genesis, development and metastasis, also their association between each other. It can provide valuable molecule index to clinical diagnoses and prognoses.Methods:1 Methylation specific PCR (MSP) method was used to examine the methylation status of E-cadherin gene in tumors and corresponding non-cancerous renal tissue.2 Immunohistochemistry was used to examine the expression of E-cadherin andβ-catenin in 53 specimens of renal cell carcinoma tissue and 53 specimens of adjacent non-tumor renal tissue.3 SPSS 11.5 was applied to analyze the results of experiment. Results:1 E-cadherin gene was methylated in 38 of 53(71.69%) RCC specimens, which was significantly higher than that in corresponding normal tissues 18.86%(10/53)(P<0.001). Methylation frequencies of E-cadherin gene had difference in different age and gender groups, but no significance (P>0.05). Methylation frequencies of E-cadherin gene in lymph node metastasis group 75.00%(9/12) was higher than that in no lymph node metastasis group 70.73%(29/41), and methylation frequencies of E-cadherin gene inⅠ,Ⅱstage 83.33%(25/30) was higher thanⅢ,Ⅳstage 56.52%(13/23), all of them show significant difference (P>0.05).2 The positive expression rate of E-cadherin protein in 16.98%(9/53) RCC specimens, which was significantly lower than that in corresponding normal tissues 84.91%(45/53)(P<0.001). The positive expression rate of E-cadherin protein had difference in different age and gender groups, but no significance (P>0.05). The positive expression rate of E-cadherin protein in lymph node metastasis group 16.67%(2/12)was lower than that in no lymph node metastasis group 17.07%(7/41), and The positive expression rate of E-cadherin protein inⅠ,Ⅱstage 17.39%(4/23) was higher thanⅢ,Ⅳstage 16.67%(5/30),but all of them did not show significant difference (P>0.05).3 The positive expression rate ofβ-catenin protein in 22.64%(12/53) RCC specimens, which was significantly lower than that in corresponding normal tissues 88.68%(47/53)(P<0.001). The positive expression rate ofβ-catenin protein had difference in different age and gender groups, but no significance (P>0.05). The positive expression rate ofβ-catenin protein in lymph node metastasis group 6.25%(6/12)was lower than that in no lymph node metastasis group 29.73%(6/35), all of them show significant difference (P>0.05).and The positive expression rate ofβ-catenin protein inⅠ,Ⅱstage 26.09%(6/23) was higher thanⅢ,Ⅳstage 20.00%(6/30), but all of them did not show significant difference (P>0.05).4 Between gene level and protein level, There were negative correlations between E-cadherin gene methylation and expression ofβ-catenin protein in renal cell carcinoma tissues (r=-0.361,P <0.05). There was a positive correlation between E-cadherin protein andβ-catenin protein in renal cell carcinoma tissues (r= 0.716,P <0.001). Between gene level and protein level, There were negative correlations between E-cadherin gene methylation and expression of E-cadherin protein in renal cell carcinoma tissues (r= -0.296,P <0.05).Conclusions:1 The methylation frequencies of E-cadherin in renal cell carcinoma were all significantly higher than that in corresponding non-cancerous renal tissues, indicating that the methylation of E-cadherin gene may be related with oncogenesis of renal cell carcinoma. It prompted that this gene methylation condition the examination possibly to have certain guiding sense to patient's prognosis appraisal.2 The expression of E-cadherin in carcinoma group was obviously lower than that in adjacent non-cancerous renal group. It indicated that E-cadherin was involved in tumorigenesis. It prompted that this gene the methylation possibly causes one which of mechanisms the protein expression drops.3 The expression ofβ-catenin in carcinoma group was obviously lower than that in adjacent non-cancerous renal group.It indicated thatβ-catenin was involved in tumorigenesis.4 E-cadherin andβ-catenin maybe collectively participated in a series of pathological progression (eg: tumorigenesis, progression, invasion and metastasis) of renal cell carcinoma.5 Besides participating cell adhesion,E-cadherin might interact with Wnt signaling pathway.It had effect on the invasion and metastasis of renal cell carcinoma through changing the intracellular distribution ofβ-catenin. It indicated that this signaling pathway was involved in tumorigenesis.