Yang Yan1, Meng-Nan Li1, Bin Yang1, Jiang Geng1, Jun-Hua Zheng1, Xu-Dong Yao2. 1. Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China. 2. Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China - drxudong_yao@126.com.
Abstract
BACKGROUND: Urothelial carcinoma (UC) is a major health problem in the general population. We aimed to evaluate the function of GFRα3 and unravel its underlying molecular mechanism to develop novel treatment options equivalent to UC. METHODS: To evaluate the function of GFRα3, a group of 60 pairs of UC patients were recruited in for this study. UC tissues and their adjacent normal control tissues (NCTs) were collected between 2012 and 2015. We used immunohistochemistry to analyze the correlation between GFRα3 expression and clinicopathologic variables and patient survival. The role of regulation of GFRα3 in UC was applied in vitro. In addition, we further investigated the signaling pathway of GFRα3 in UC progression. RESULTS: The expression level of GFRα3 was remarkably upregulated in 49.3% (19/60) patients and downregulated in 25.0% (15/60) patients. The GFRα3 protein expression was upregulated in UC tissues. GFRα3 promotes UC cell migration and invasion in vitro. GFRα3 also promotes UC cell metastasis in vitro. High level of GFRα3 promotes UC cell migration via upregulation of MMP9 expression. CONCLUSIONS: Our results demonstrate that increased GFRα3 expression is significantly correlated with poor prognosis of patients with UC. Thus, GFRα3 might be an important marker and a therapeutic target for UC.
BACKGROUND:Urothelial carcinoma (UC) is a major health problem in the general population. We aimed to evaluate the function of GFRα3 and unravel its underlying molecular mechanism to develop novel treatment options equivalent to UC. METHODS: To evaluate the function of GFRα3, a group of 60 pairs of UC patients were recruited in for this study. UC tissues and their adjacent normal control tissues (NCTs) were collected between 2012 and 2015. We used immunohistochemistry to analyze the correlation between GFRα3 expression and clinicopathologic variables and patient survival. The role of regulation of GFRα3 in UC was applied in vitro. In addition, we further investigated the signaling pathway of GFRα3 in UC progression. RESULTS: The expression level of GFRα3 was remarkably upregulated in 49.3% (19/60) patients and downregulated in 25.0% (15/60) patients. The GFRα3 protein expression was upregulated in UC tissues. GFRα3 promotes UC cell migration and invasion in vitro. GFRα3 also promotes UC cell metastasis in vitro. High level of GFRα3 promotes UC cell migration via upregulation of MMP9 expression. CONCLUSIONS: Our results demonstrate that increased GFRα3 expression is significantly correlated with poor prognosis of patients with UC. Thus, GFRα3 might be an important marker and a therapeutic target for UC.