Abstract

BackgroundGlutamine-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.MethodsWe 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.ResultsGFPT1 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).ConclusionsGFPT1 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.

Highlights

  • Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies with a dismal survival rate and is estimated to become the second leading cause of cancer-related death in the USA by 2030 [1]

  • Glutamine-fructose-6-phosphate transaminase 1 (GFPT1) expression is upregulated in pancreatic ductal adenocarcinoma (PDAC) To investigate the role of GFPT1 in pancreatic tumorigenesis, we examined the mRNA expression levels of GFPT1 in pancreatic tumor and normal tissues by analyzing Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and GenotypeTissue Expression (GTEx) dataset analyses

  • Association between GFPT1 levels and clinicopathological characteristics in resectable PDAC patients To investigate the clinicopathological significance of GFPT1 mRNA expression in PDAC tissues, we assayed the relative GFPT1 expression using quantitative polymerase chain reaction (PCR) and further assessed the relationship between GFPT1 expression and clinicopathological characteristics in 134 resectable PDAC samples who all underwent radical surgical resection

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Summary

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies with a dismal survival rate and is estimated to become the second leading cause of cancer-related death in the USA by 2030 [1]. Since early-stage PDAC generally lacks clinical symptoms, less than 20% of patients are eligible for initial surgical resection, as they are diagnosed at a late stage [3, 4]. Nearly 80% of PDAC patients experience local recurrence or distant metastases within 2 years of a potential curative resection, mostly because of the presence of micrometastases before the initial resection [5]. 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). We investigated the prognostic significance of GFPT1 expression in patients with resectable PDAC

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