Yitao Gong1,2,3,4, Yunzhen Qian1,2,3,4, Guopei Luo1,2,3,4, Yu Liu1,2,3,4, Ruijie Wang1,2,3,4, Shengming Deng1,2,3,4, He Cheng1,2,3,4, Kaizhou Jin1,2,3,4, Quanxing Ni1,2,3,4, Xianjun Yu1,2,3,4, Weiding Wu5,6,7,8, Chen Liu9,10,11,12. 1. Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No.270 DongAn Road, Shanghai, 200032, China. 2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. 3. Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China. 4. Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China. 5. Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No.270 DongAn Road, Shanghai, 200032, China. weidingwu@126.com. 6. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. weidingwu@126.com. 7. Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China. weidingwu@126.com. 8. Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China. weidingwu@126.com. 9. Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No.270 DongAn Road, Shanghai, 200032, China. liuchen@fudanpci.org. 10. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. liuchen@fudanpci.org. 11. Shanghai Pancreatic Cancer Institute, Shanghai, 200032, China. liuchen@fudanpci.org. 12. Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, China. liuchen@fudanpci.org.
Abstract
BACKGROUND: Glutamine-fructose-6-phosphate transaminase 1 (GFPT1) is the first rate-limiting enzyme of the hexosamine biosynthesis pathway (HBP), which plays a pivotal role in the progression of pancreatic ductal adenocarcinoma (PDAC). Therefore, we investigated the prognostic significance of GFPT1 expression in patients with resectable PDAC. METHODS: We analyzed public datasets to compare GFPT1 expression in tumor tissues and normal/adjacent pancreatic tissues. We measured the relative GFPT1 expression of 134 resected PDAC specimens in our institution, using real-time polymerase chain reaction (PCR). Survival was compared between high and low GFPT1 expression groups using Kaplan-Meier curves and log-rank tests. Multivariate analyses were estimated using Cox regression and logistic regression models. RESULTS: GFPT1 is generally upregulated in PDAC tissues, according to the analysis of public datasets. The data from our institution shows that high GFPT1 expression was correlated with a high rate of lymph node (LN) metastasis (p = 0.038) and was an independent risk factor for LN metastasis (odds ratio (OR) = 3.14, 95% confidence interval (CI) = 1.42 to 6.90, P = 0.005). High GFPT1 expression was significantly associated with poor overall survival (OS; P = 0.019) in patients with resected PDAC. The multivariable-adjusted hazard ratio (HR) for mortality when comparing patients with high and low GFPT1 expression was 2.54 (95% CI = 1.35 to 4.79, P = 0.004). CONCLUSIONS: GFPT1 is generally upregulated in PDAC tissue and is associated with a high risk of LN metastasis and an unfavorable outcome in patients with resectable PDAC, suggesting its crucial role in PDAC progression.
BACKGROUND: Glutamine-fructose-6-phosphate transaminase 1 (GFPT1) is the first rate-limiting enzyme of the hexosamine biosynthesis pathway (HBP), which plays a pivotal role in the progression of pancreatic ductal adenocarcinoma (PDAC). Therefore, we investigated the prognostic significance of GFPT1 expression in patients with resectable PDAC. METHODS: We analyzed public datasets to compare GFPT1 expression in tumor tissues and normal/adjacent pancreatic tissues. We measured the relative GFPT1 expression of 134 resected PDAC specimens in our institution, using real-time polymerase chain reaction (PCR). Survival was compared between high and low GFPT1 expression groups using Kaplan-Meier curves and log-rank tests. Multivariate analyses were estimated using Cox regression and logistic regression models. RESULTS: GFPT1 is generally upregulated in PDAC tissues, according to the analysis of public datasets. The data from our institution shows that high GFPT1 expression was correlated with a high rate of lymph node (LN) metastasis (p = 0.038) and was an independent risk factor for LN metastasis (odds ratio (OR) = 3.14, 95% confidence interval (CI) = 1.42 to 6.90, P = 0.005). High GFPT1 expression was significantly associated with poor overall survival (OS; P = 0.019) in patients with resected PDAC. The multivariable-adjusted hazard ratio (HR) for mortality when comparing patients with high and low GFPT1 expression was 2.54 (95% CI = 1.35 to 4.79, P = 0.004). CONCLUSIONS: GFPT1 is generally upregulated in PDAC tissue and is associated with a high risk of LN metastasis and an unfavorable outcome in patients with resectable PDAC, suggesting its crucial role in PDAC progression.
Authors: Leandro M Colli; Mitchell J Machiela; Han Zhang; Timothy A Myers; Lea Jessop; Olivier Delattre; Kai Yu; Stephen J Chanock Journal: Cancer Res Date: 2017-04-26 Impact factor: 12.701
Authors: Lola Rahib; Benjamin D Smith; Rhonda Aizenberg; Allison B Rosenzweig; Julie M Fleshman; Lynn M Matrisian Journal: Cancer Res Date: 2014-06-01 Impact factor: 12.701