High GFPT1 expression predicts unfavorable outcomes in patients with resectable pancreatic ductal adenocarcinoma

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.