High expression of GFAT1 predicts unfavorable prognosis in patients with hepatocellular carcinoma

// Lili Li 1, 2, * , Miaomiao Shao 1, 2, * , Peike Peng 1, 2 , Caiting Yang 1, 2 , Shushu Song 1, 2 , Fangfang Duan 1, 2, 3 , Dongwei Jia 1, 2 , Mingming Zhang 1, 2 , Junjie Zhao 4 , Ran Zhao 3 , Weicheng Wu 1, 2 , Lan Wang 1, 2, 3 , Can Li 1, 2 , Hao Wu 1, 2 , Jie Zhang 1, 2, 3 , Xin Wu 5 , Yuanyuan Ruan 1, 2 , Jianxin Gu 1, 2, 3 1 Key Laboratory of Glycoconjugate Research Ministry of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai, P.R.China 2 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, P.R.China 3 Institutes of Biomedical Sciences, Fudan University, Shanghai, P.R.China 4 Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, P.R.China 5 Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University Shanghai, P.R.China * These authors contribute equally to this work Correspondence to: Yuanyuan Ruan, email: yuanyuanruan@fudan.edu.cn Xin Wu, email: sky_xin1980@aliyun.com Keywords: GFAT1, hepatocellular carcinoma, overall survival, recurrence, prognostic factor Received: June 15, 2016      Accepted: January 23, 2017      Published: February 07, 2017 ABSTRACT Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. As a branch of glucose metabolism, hexosamine biosynthesis pathway (HBP) has been reported to play a critical role in the insulin resistance and progression of cancer. Glutamine:fructose-6-phosphate amidotransferase (GFAT) is the rate-limiting enzyme of the HBP; nevertheless, the prognostic value of GFAT1 in HCC remains elusive. In this study, we found that high expression of GFAT1 was significantly associated with serum alpha-fetoprotein (AFP), serum alanine aminotransferase (ALT), tumor size, tumor encapsulation, T stage and TNM stage. High GFAT1 expression was identified as an independent prognostic factor which predicted poor overall survival (OS) and recurrence-free survival (RFS) in HCC patients. Incorporation of GFAT1 expression could improve the prognostic accuracy of traditional TNM stage system. Integration of GFAT1 expression with other independent prognosticators generated a predictive nomogram, which showed better prognostic efficiency for OS and RFS in HCC patients. In vitro studies also revealed that GFAT1 promoted the proliferation, cell cycle progression, migration and invasion of HCC cells. In conclusion, GFAT1 is a potential prognostic biomarker for overall survival and recurrence-free survival of HCC patients after surgery.