High expression of GFAT1 predicts unfavorable prognosis in patients with hepatocellular carcinoma
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Lili Li1,2,*, Miaomiao Shao1,2,*, Peike Peng1,2, Caiting Yang1,2, Shushu Song1,2, Fangfang Duan1,2,3, Dongwei Jia1,2, Mingming Zhang1,2, Junjie Zhao4, Ran Zhao3, Weicheng Wu1,2, Lan Wang1,2,3, Can Li1,2, Hao Wu1,2, Jie Zhang1,2,3, Xin Wu5, Yuanyuan Ruan1,2, Jianxin Gu1,2,3
1Key Laboratory of Glycoconjugate Research Ministry of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai, P.R.China
2Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, P.R.China
3Institutes of Biomedical Sciences, Fudan University, Shanghai, P.R.China
4Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, P.R.China
5Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University Shanghai, P.R.China
*These authors contribute equally to this work
Yuanyuan Ruan, email: [email protected]
Xin Wu, email: [email protected]
Keywords: GFAT1, hepatocellular carcinoma, overall survival, recurrence, prognostic factor
Received: June 15, 2016 Accepted: January 23, 2017 Published: February 07, 2017
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.
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