Low FAT4 expression is associated with a poor prognosis in gastric cancer patients

// Xiaoting Jiang 1 , Zhengchuang Liu 1 , Yingjie Xia 1 , Jungang Luo 1 , Ji Xu 2 , Xujun He 1 and Houquan Tao 1, 2 1 Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang, China 2 Department of Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang, China Correspondence to: Houquan Tao, email: taohouquan2008@aliyun.com Xujun He, email: hxj0105099@163.com Keywords: FAT4; gastric cancer; prognosis; methylation; distant metastasis Received: April 15, 2017     Accepted: December 11, 2017     Published: December 26, 2017 ABSTRACT In this study, we investigated the role of Fat atypical cadherin 4 (FAT4) in gastric cancer (GC) progression. Immunohistochemical analysis showed lower FAT4 expression in tumor tissues from GC patients than in normal gastric epithelium. Lower FAT4 expression was associated with poor prognosis, tumor size and invasion, and lymph node and distant metastases. Multivariate analysis showed that TNM stage, lymph node and distant metastases, Lauren classification, and FAT4 expression were independent prognostic factors in GC. Methylation-specific PCR analysis showed increased FAT4 promoter methylation in GC tumor tissues and cell lines. Higher FAT4 promoter methylation was associated with low FAT4 expression and a poor prognosis. BGC-823 cells showed increased FAT4 expression upon treatment with 5-azacytidine, demethylating agent. FAT4 knockdown in BGC-823 cells led to increased cell proliferation, migration and invasiveness. Moreover, xenografts of BGC-823 cells with FAT4 knockdown showed enhanced tumor growth and metastasis in nude mice. These findings demonstrate that low FAT4 expression is associated with a poor prognosis in GC patients.