Relationship Between Expression Of TGR5 And EMT Of Cholangiocarcinoma And Its Value In Prognosis Evaluation

Objective: To investigate the relationship between the expression of bile acid receptor TGR5 and epithelial-mesenchymal transition(EMT)in cholangiocarcinoma cells,and to analyze the relationship between the expression of TGR5 in cholangiocarcinoma and the histopathological grade and prognosis of cholangiocarcinoma.Methods: A total of 59 cases of hepatic hilar cholangiocarcinoma specimens and clinical data were collected from the General Surgery Center of the Western Theater Command Hospital from January 2013 to January2018.The expression levels of TGR5 and EMT-related markers(E-cadherin,vimentin,N-cadherin,CK19 and ZEB1)were detected by immunohistochemistry.Correlation between TGR5 and EMT-related markers in hilar cholangiocarcinoma was analyzed by Pearson correlation coefficient.Spearman correlation coefficient was used to analyze the correlation between TGR5 expression and histopathological parameters in hilar cholangiocarcinoma.Using the follow-up data collected by the clinical research center of the department,the factors affecting prognosis were screened by univariate analysis,and then the Cox proportional hazards regression model was used to analyze the relationship between the expression level of TGR5 and the tumor-free survival rate and total survival rate of patients.The test level was statistically significant at P < 0.05.Results: The expression of bile acid receptor TGR5 in hepatic hilar cholangiocarcinoma was negatively correlated with the expression of EMT-related markers: E-cadherin(r=-0.718,P<0.01),CK19(r=-0.774,P<0.01),while N-cadherin(r=0.817,P <0.01),vimentin(r=0.763,P <0.01),ZEB1(r=0.698,P <0.01)showed a positive correlation.TGR5 was positively correlated with the pathological grade of hilar cholangiocarcinoma(r=0.850,P<0.01).As the expression of TGR5 was up-regulated,a lower degree of differentiation was observed in hilar cholangiocarcinoma.In terms of prognosis,TGR5 was an independent factor affecting tumor-free survival and overall survival(P <0.01),with the former HR=15.298(95% CI:3.893-60.121),the latter HR =6.906(95% CI: 2.244-21.248).Conclusion: Bile acid may induce epithelial-mesenchymal transition in cholangiocarcinoma cells through bile acid membrane receptor TGR5,which may be beneficial to the invasion and metastasis of cholangiocarcinoma and affect the prognosis of patients.(1)The expression of TGR5 is correlated with EMT in cholangiocarcinoma tissues.In hilar cholangiocarcinoma,TGR5 expression was negatively correlated with EMT epithelial marker expression and positively correlated with mesenchymal cell markers.We hypothesized that bile acids may induce epithelial-mesenchymal transition in cholangiocarcinoma cells via the bile acid receptor TGR5.(2)As the expression of TGR5 is up-regulated,hepatic hilar cholangiocarcinoma tissue is observed to have a lower degree of differentiation and is positively correlated with lymphatic metastasis.We speculate that this is associated with stronger migration and invasion biological behavior in high TGR5-expressing cholangiocarcinoma cells.(3)The expression of TGR5 was negatively correlated with the patient's total survival time and tumor-free survival time.Detection of TGR5 expression in postoperative cholangiocarcinoma may be helpful indetermining the prognosis of patients with cholangiocarcinoma.