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

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.

Tissue metabolomics identified new biomarkers for the diagnosis and prognosis prediction of pancreatic cancer

“…Emerging evidence has revealed that amino acid metabolism plays an important role in PC initiation and progression (31)(32)(33). Consistent with former studies, several amino acid transporters were also found to be highly expressed in PC tumor tissues to satisfy the increased need for proliferation (Figure 3B), such as cytoplasmic aspartate transaminase (GOT1) (34), proline oxidase (PRODH1) (35), and glutamine fructose 6-phosphate amidotransferase-1 (GFPT1) (36)(37)(38).…”

The prognostic value of intratumoral and peritumoral tumor-infiltrating FoxP3+Treg cells in of pancreatic adenocarcinoma: a meta-analysis

“…The prognosis of patients with pancreatic cancer is very poo r[ 41 , 42 ]. The NEJM [ 43 ] and other magazines have reported that the monoclonal antibody drug blocking immunoassay (such as PD-1 and PD-L1) is effective for treating non-small cell lung cancer, malignant melanoma, renal cell carcinoma, ovarian cancer, stomach cancer, and breast cancer.…”

Mucin 1 expression is regulated by hsa_circ_0055054/microRNA‑122‑5p and promotes hepatocellular carcinoma development

“…The hsa_circ_0055054 is formed through the cyclization of exons 10–11 of the glucosamine-fructose-6-phosphate aminotransferase isomerizing 1 (GFPT1) gene. Previous studies have reported that GFPT1 may contribute to the progression of cervical ( 43 ), pancreatic ( 44 ) and esophageal cancer ( 45 ), but the function of hsa_circ_0055054 remains unknown. The present study demonstrated that the expression of hsa_circ_0055054 was significantly higher in HCC tissues compared with the corresponding adjacent normal tissues, and that it binds to miR-122-5p.…”