The combination of YAP/TAZ predicts the clinical prognosis in patients with cholangiocarcinoma after radical resection

Abstract

Objective: Cholangiocarcinoma (CCA) is a malignant tumor derived from bile duct epithelial cells with extremely poor prognosis. The Hippo-Yes-associated protein (YAP)/transcription activator with PDZ binding motif (TAZ) signaling plays a critical role in cancer stem cell biology. Previous studies have shown that the positive expression of YAP/TAZ in CCA predicts larger tumor size and unfavorable clinical outcomes. We aim to evaluate the prognostic value of YAP/TAZ detection in CCA patients. Methods: CCA patients who underwent radical resection were retrospectively analyzed at our institution from January 2011 to June 2016. Postoperative pathological specimens were scored by YAP/TAZ immunohistochemical staining. The prognostic value of YAP/TAZ was analyzed by multivariate Cox-proportional hazards model. Results: A total of 91 CCA patients were enrolled. During a median follow-up time of 11.0 months, 69.2% patients relapsed and 45.1% died. The median OS and DFS were 10.7 months and 8.8 months respectively. The YAP/TAZ dual positive patients owned a worse TNM stage (P=0.015), poorer tissue differentiation (P=0.007), and a higher CA199 than those in negative patients. Multivariate Cox analysis identified that YAP/TAZ dual positivity as a significant factor predicted poorer OS (P=0.010) and DFS (P=0.028) in CCA patients after radical resection. In subgroup analysis, YAP/TAZ combination also significantly predicted OS (P=0.044) and DFS (P=0.043) in CCA patients with positive lymphatic metastasis and/or surgical margin who required adjuvant therapy. Conclusions: YAP/TAZ positivity is an independent predictive factor for survival in CCA patients after radical resectiony.