Increased α1-3 fucosylation of α-1-acid glycoprotein (AGP) in pancreatic cancer.

Balmaña, Meritxell; Giménez, Estela; Puerta, Angel; Llop Escorihuela, Esther; Figueras, Joan; Fort, Esther; Sanz-Nebot, Victoria; Bolos Pi, Ma. Carmen de; Rizzi, Andreas; Barrabés, Sílvia; Frutos, Mercedes de; Peracaula, Rosa

doi:http://dx.doi.org/10.1016/j.jprot.2015.11.006

Increased α1-3 fucosylation of α-1-acid glycoprotein (AGP) in pancreatic cancer.

Citation

Balmaña M, Giménez E, Puerta A, Llop E, Figueras J, Fort E. et al. Increased α1-3 fucosylation of α-1-acid glycoprotein (AGP) in pancreatic cancer. J Proteomics. 2016 Jan 30;132:144-54. doi: 10.1016/j.jprot.2015.11.006.

Abstract

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 including mass 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.