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

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

This work was supported by the Government of Catalonia (grant 2014 SGR 229), the Spanish Ministry of Science and Innovation (grant BIO 2010-16922, awarded to R. P) and the Spanish Ministry of Economy and Competitiveness (grant CTQ2013-43236, awarded to M.F. and grant CTQ2011-27130, awarded to V. S-N)

Elsevier

Manager: Ministerio de Ciencia e Innovación (Espanya)
Author: Balmaña, Meritxell
Giménez, Estela
Puerta, Angel
Llop Escorihuela, Esther
Figueras, Joan
Fort Martorell, Esther
Sanz Nebot, María Victoria
Bolòs, Carme de
Rizzi, Andreas
Barrabés Vera, Sílvia
Frutos, Mercedes de
Peracaula Miró, Rosa
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 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
This work was supported by the Government of Catalonia (grant 2014 SGR 229), the Spanish Ministry of Science and Innovation (grant BIO 2010-16922, awarded to R. P) and the Spanish Ministry of Economy and Competitiveness (grant CTQ2013-43236, awarded to M.F. and grant CTQ2011-27130, awarded to V. S-N)
Format: application/pdf
Document access: http://hdl.handle.net/10256/12463
Language: eng
Publisher: Elsevier
Collection: info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jprot.2015.11.006
info:eu-repo/semantics/altIdentifier/issn/1874-3919
info:eu-repo/grantAgreement/MICINN//BIO2010-16922/ES/GLICOSILACION ALTERADA EN CANCER: GLICOPROTEINAS Y GLICOSILTRANSFERASAS EN SUERO Y EN TEJIDOS COMO MARCADORES TUMORALES/
Rights: Tots els drets reservats
Subject: Pàncrees -- Càncer
Pancreas -- Cancer
Marcadors tumorals
Tumor markers
Title: Increased α1-3 fucosylation of α-1-acid glycoprotein (AGP) in pancreatic cancer
Type: info:eu-repo/semantics/article
Repository: DUGiDocs

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