title: Increased α1-3 fucosylation of α-1-acid glycoprotein (AGP) in pancreatic cancer.
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.
authors.affiliation: Biochemistry and Molecular Biology Unit, Department of Biology, University of Girona, Girona, Spain.
authors.forename: Meritxell
authors.initials: M
authors.lastname: Balmaña
authors.affiliation: Department of Analytical Chemistry, University of Barcelona, Barcelona, Spain.
authors.forename: Estela
authors.initials: E
authors.lastname: Giménez
authors.affiliation: Institute of Organic Chemistry (IQOG-CSIC), Madrid, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Puerta
authors.affiliation: Biochemistry and Molecular Biology Unit, Department of Biology, University of Girona, Girona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Llop
authors.affiliation: Department of Surgery, Dr. Josep Trueta University Hospital, IdIBGi, Girona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Figueras
authors.affiliation: Department of Gastrointestinal, Dr. Josep Trueta University Hospital, Girona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Fort
authors.affiliation: Department of Analytical Chemistry, University of Barcelona, Barcelona, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Sanz-Nebot
authors.affiliation: Gastroesophagic Cancer Research Group, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
authors.forename: Carme
authors.initials: C
authors.lastname: de Bolós
authors.affiliation: Department of Analytical Chemistry, University of Vienna, Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Rizzi
authors.affiliation: Biochemistry and Molecular Biology Unit, Department of Biology, University of Girona, Girona, Spain.
authors.forename: Sílvia
authors.initials: S
authors.lastname: Barrabés
authors.affiliation: Institute of Organic Chemistry (IQOG-CSIC), Madrid, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: de Frutos
authors.affiliation: Biochemistry and Molecular Biology Unit, Department of Biology, University of Girona, Girona, Spain. Electronic address: rosa.peracaula@udg.edu.
authors.forename: Rosa
authors.initials: R
authors.lastname: Peracaula
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000097:blood*; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D005643:Fucose / Q000097:blood; D006031:Glycosylation; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000097:blood*; D009961:Orosomucoid / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D009961:Orosomucoid; D005643:Fucose
keywords: Aleuria aurantia lectin (AAL); Capillary electrophoresis; Fucosylation; Mass spectrometry; Pancreatic cancer; α-1-acid glycoprotein