Wnt Antagonist SFRP1 In Lung Adenocacinoma Tumorigenesis And Metastasis

Objective:1.To investigate the expression of SFRP1 gene methylation and SFRP1 protein in lung adenocarcinoma.2.To investigate the expression of SFRP1,beta-catenin and E-cadherin in lung adenocarcinoma and its clinicopathological parameters.Methods:1.MaterialsThere were 60 lung adenocarcinoma patients who underwent a completely surgical excision from May 2015 to May 2016 in Wuhan General Hospital of PLA.One specimen was fixed in 10%formalin solution,embedded by Paraffin.Among these samples,some fresh specimens and corresponding tissue samples were stored at-80? immediately after resection until the extraction of protein and RNA.The clinical data included 37 males and 23 females.The patients' age are from 41 to 76.According to the lung cancer TNM clinical staging criteria revised by 2009 International Association for the study of lung cancer(IASLC):clinical stage ?+?in 40 cases,clinical stage ? in 20 cases,high and middle differentiation in 26 cases,low differentiation in 34 cases,no lymph node metastasis in 39 cases,lymph node metastasis in 21 cases.All cases did not receive chemoradiotherapy before operation and all the resected specimens were confirmed by routine pathology.2.Methylation Specific PCR(MSP),RT-PCR and Immunohistochemistry Statistical Analysis:Statistical analysis were performed using the SPSS 20.0.Result:1.Positive methylation rate of SFRP1 gene in lung adenocarcinoma and adjacent tissues.Positive methylation rate of SFRP1 gene in lung adenocarcinoma and adjacent tissues were 58.3%,20.0%respectively(?2=11.849,P =0.001).The methylation of SFRP1 gene was significantly correlated with the differentiation degree and lymph node metastasis of lung adenocarcinoma.2.Expression of SFRP1,beta-catenin and E-cadherin in lung adenocarcinoma and adjacent tissues.The positive expression rates of SFRP1 protein in lung adenocarcinoma and adjacent tissues were 38.3%,83.3%respectively(P<0.05).The abnormal expression rates of ?-catenin in lung adenocarcinoma and adjacent tissues were 75.0%,3.3%respectively(P<0.05).The negative expression rates of E-cadherin in lung adenocarcinoma and adjacent tissues were 58.3%,6.7%respectively(P<0.05).3.Expression of SFRP1mRNA,beta-catenin mRNA and E-cadherin mRNA in lung adenocarcinoma and adjacent tissues.The relative expression of SFRP1mRNA were 0.847±0.297,2.019±0.445 in lung adenocarcinoma tissues and adjacent tissues respectively.The expression of SFRP1mRNA in lung adenocarcinoma was lower than that in adjacent tissues(t=-4.386,P<0.01).The relative expression of ?-catenin mRNA were 0.883±0.167,0.524±0.193 in lung adenocarcinoma tissues and adjacent tissues respectively.The expression of ?-catenin mRNA in lung adenocarcinoma was higher than that in adjacent tissues(t=2.818,P<0.05).The relative expression of E-cadherin mRNA were 0.877±0.274,1.568±0.488 in lung adenocarcinoma tissues and adjacent tissues respectively.The expression of E-cadherin mRNA in lung adenocarcinoma was lower than that in adjacent tissues(t =-2.467,P<0.05).4.Correlation of SFRP1,beta-catenin and E-cadherin protein expression in lung adenocarcinoma.The positive expression of SFRP1 was negatively correlated with the abnormal expression of ?-catenin protein(r=-0.495,P<0.05).The abnormal expression of?-catenin was positively correlated with the negative expression of E-cadherin protein(r=0.527,P<0.001).5.Correlation analysis of methylation and protein expression of SFRP1 gene.30 cases with SFRP1 protein negative expression were in 35 cases of SFRP1 gene methylation positive expression.7 cases with SFRP1 protein absent expression were in 25 cases of SFRP1 gene methylation negative expression.Methylation of SFRP1 gene was correlated with SFRP1 protein expression deletion(r=-0.585,P<0.001).6.Relationship between SFRP1,beta-catenin,E-cadherin expression and clinicopathological features of lung adenocarcinoma.The positive expression rate of SFRP1 protein,the abnormal expression rate of?-catenin protein and the negative expression rate of E-cadherin protein were related to tumor differentiation,TNM stage and lymph node metastasis(P<0.05).Conclusion:1.The decrease of SFRP1 protein expression may be due to SFRP1 gene methylation.Expression of SFRP1 gene methylation and protein are associated with degree of differentiation and lymph node metastasis.2.Low expression of SFRP1 may be related to the accumulation of ?-catenin in cytoplasm/nucleus.The positive expression of SFRP1 and the abnormal expression of ?-catenin may be related to the development and metastasis of lung adenocarcin-oma.The aggregation of ?-catenin in cytoplasm/nucleus may cause the decrease of E-cadherin expression,resulting in the decrease of E-cadherin complex formation and the development and metastasis of lung adenocarcinoma.