Low FAT4 expression is associated with a poor prognosis in gastric cancer patients
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Xiaoting Jiang1, Zhengchuang Liu1, Yingjie Xia1, Jungang Luo1, Ji Xu2, Xujun He1 and Houquan Tao1,2
1Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang, China
2Department of Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang, China
Houquan Tao, email: [email protected]
Xujun He, email: [email protected]
Keywords: FAT4; gastric cancer; prognosis; methylation; distant metastasis
Received: April 15, 2017 Accepted: December 11, 2017 Published: December 26, 2017
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.
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