Increased α1-3 fucosylation of α-1-acid glycoprotein (AGP) in pancreatic cancer
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Pancreatic cancer (PDAC) lacks reliable diagnostic biomarkers and the search for new biomarkers represents an important
challenge. Previous results looking at a small cohort of patients showed an increase in α-1-acid glycoprotein
(AGP) fucosylation in advanced PDAC using N-glycan sequencing. Here,we have analysed AGP glycoforms in a larger
cohort using several analytical techniques includingmass spectrometry (MS), capillary zone electrophoresis (CZE) and
enzyme-linked lectin assays (ELLAs) for determining AGP glycoforms which could be PDAC associated. AGP from 31
serum samples, including healthy controls (HC), chronic pancreatitis (ChrP) and PDAC patients, was purified by immunoaffinity
chromatography. Stable isotope labelling of AGP released N-glycans and their analysis by zwitterionic
hydrophilic interaction capillary liquid chromatography electrospray MS (μZIC-HILIC–ESI-MS) showed an increase
in AGP fucosylated glycoforms in PDAC compared to ChrP and HC. By CZE-UV analysis, relative concentrations of
some of the AGP isoforms were found significantly different compared to those in PDAC and HC. Finally, ELLAs
using Aleuria aurantia lectin displayed a significant increase in AGP fucosylation, before and after AGP neuraminidase
treatment, in advanced PDAC compared to ChrP and HC, respectively. Altogether, these results indicate that α1-3
fucosylated glycoforms of AGP are increased in PDAC and could be potentially regarded as a PDAC biomarker
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