The Expression Of TAZ In Adenocarcinoma Of The Esophagogastric Junction And Its Clinical Significance

Objective:TAZ is a downstream agent of Hippo signal pathway. β-catenin is a cell adhesion molecule associated with the invasion and metastasis of carcinomas as well as a critical component of Wnt pathway. TAZ and P-catenin have long been thought to play a vital role in tumour development and progression. This study aimed to detect expressions of TAZ and β-catenin in adenocarcinoma of the esophagogastric junction (AEG) and discuss their relationship with clinicopathological features of AEG patients. Finally, we explore their clinicopathological significance.Methods:The expression of TAZ and β-catenin were detected by immunohistochemistry(PV-9000) of 135 AEG samples, and analyzed with complete clinicopathological features. Compared the expression result of TAZ and β-catenin in AEG with 37 normal mucosa and 41 dysplasia samples of esophagogastric junction (EGJ). Kruskal-Wallis test was used to assess the difference of TAZ and β-catenin in the three groups. The relationship between TAZ or β-catenin expression and clinicopathologic parameters were analyzed using Chi-square test and T test. The correlation between TAZ and β-catenin was analyzed using the spearman’s rank test. Overall survival rates of AEG patients were also calculated using the Kaplan-Meier method. Cox proportional hazard model (univariate and multivariate) was performed to assess the prognostic values, were studied comparably.Results:1.TAZ protein showed a strictly nuclear staining pattern in AEG and dysplasia with IHC. Expression of TAZ was higher in dysplasia and AEG compared with normal mucosa (P<0.001,0.008). The positive expression rate of nuclear β-catenin was significantly higher in carcinoma and dysplasia than in normal mucosa (P<0.001,=0.046). Abnormal expression rate of membranous β-catenin in AEG was significantly higher than in normal mucosa tissues and dysplasia (P=0.001,0.002).2.In AEG, over expression of TAZ was directly correlated with abnormal nuclear β-catenin expression (r=0.298, P<0.001) and membranous β-catenin (r=0.202, P=0.019).3.Patients with abnormal TAZ or β-catenin expression of AEG exhibited a shorter overall survival (OS) and lower overall survival rate than those with normal TAZ or β-catenin expression (P<0.05). In addition, patients with abnormal expression of both TAZ and β-catenin exhibited worst overall survival.In multivariate survival analysis, abnormal expression of TAZ(Hazard rate (HR) 1.879, CI 95%,1.079-3.218, P=0.022), TAZ & β-catenin (nuclear and membranous) (HR 1.899, CI 95%,1.053-3.423, P=0.033)and tumour differentiation(HR 1.870, CI 95%,1.216-2.877, P= 0.004) were found to be independent prognostic factors related to OS of AEG patients.Conclusions:Over expression of TAZ was associated with abnormal expression of β-catenin, which is correlated with the poor prognosis of patients with AEG. Abnormal expression of TAZ and TAZ & P-catenin (nuclear and membranous) are independent prognostic factors, so targeting TAZ and β-catenin could prove to be a promising therapeutic strategy for the treatment of AEG.