Low expression of Rap1GAP is associated with epithelial-mesenchymal transition (EMT) and poor prognosis in gastric cancer

// Ya Yang 1, 4, * , Jia Zhang 1, * , Yan Yan 1 , Hui Cai 2 , Min Li 1 , Kai Sun 1 , Jizhao Wang 1 , Xu Liu 1 , Jiansheng Wang 1 , Xiaoyi Duan 3 1 The Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China 2 Department of Vascular Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China 3 Department of Radiology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China 4 Department III of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, Henan, China * These authors have contributed equally to this work Correspondence to: Xiaoyi Duan, email: duanxy@mail.xjtu.edu.cn Jiansheng Wang, email: wangjsh@mail.xjtu.edu.cn Keywords: gastric cancer, RAP1 GTPase activating protein (Rap1GAP), E-cadherin, Matrix metalloproteinase-2, prognosis Received: October 19, 2015      Accepted: November 21, 2016      Published: December 21, 2016 ABSTRACT Rap1GAP is a crucial tumor suppressor, but its role in gastric cancer (GC) is little investigated. In this study, we found that the expression of Rap1GAP was decreased in GC. Low expression of Rap1GAP was positively correlated with advanced pTNM stage, Borrmann types, tumor diameter and poor prognosis in patients with GC. Low expression of Rap1GAP correlated with loss of E-cadherin expression, and anomalous positivity of MMP2 expression. Multivariate analysis showed that low expression of Rap1GAP was an independent prognostic factor. Ectopic expression of Rap1GAP impaired cell migration and invasion, promoted the expression of E-cadherin and decreased the expression of MMP2. These results suggest that Rap1GAP functions as a novel suppressor of EMT and tumor metastasis in GC, and loss of Rap1GAP predicts poor prognosis in GC.