High endothelin-1 expression predicts good prognosis in upper tract urothelial carcinoma

Purpose: The survival of upper tract urothelial carcinoma has not changed significantly during the last two decades and there were also no adequate prognostic factors for the disease. In this study, we aim to evaluate the predictive value of endothelin expression on the prognosis of patients with upper tract urothelial carcinoma. Methods: One hundred and fifty-six UTUC patients who underwent radical nephroureterectomy (RNU) with bladder cuff excision were enrolled in the study. ET axis expression was analyzed by immunohistochemistry. The association between retrospectivelycollectedclinical parameters and ET axis expression was examined by using the Χ² test. The Kaplan-Meier method was applied to estimate the effect of ET axis expression on metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS). Hazard ratios of ET axis expression on survival were evaluated by the Cox regression model.Results: Endothelin-1 expression was strongly associated with superficial pathologic tumor stage (P = 0.002), absence of lymph node involvement (P < 0.001), and low pathologic tumor grade (P = 0.040). Endothelin-1 overexpression was also associated with significantly better metastasis-free survival (HR = 0.40, P = 0.047), CSS (HR = 0.21, P = 0.002), and overall survival (HR = 0.35, P = 0.021). Conclusions: These findings indicate that endothelin expression could be a biomarker that predicts good survival and warrants further examination as anti-cancer treatment target. Studies focusing on the underlying mechanisms are needed to provide novel therapy for upper tract urothelial carcinoma.