title: Development of a novel system for mass spectrometric analysis of cancer-associated fucosylation in plasma α1-acid glycoprotein.
abstract: Human plasma α1-acid glycoprotein (AGP) from cancer patients and healthy volunteers was purified by sequential application of ion-exchange columns, and N-linked glycans enzymatically released from AGP were labeled and applied to a mass spectrometer. Additionally, a novel software system for use in combination with a mass spectrometer to determine N-linked glycans in AGP was developed. A database with 607 glycans including 453 different glycan structures that were theoretically predicted to be present in AGP was prepared for designing the software called AGPAS. This AGPAS was applied to determine relative abundance of each glycan in the AGP molecules based on mass spectra. It was found that the relative abundance of fucosylated glycans in tri- and tetra-antennary structures (FUCAGP) was significantly higher in cancer patients as compared with the healthy group (P < 0.001). Furthermore, extremely elevated levels of FUCAGP were found specifically in patients with a poor prognosis but not in patients with a good prognosis. In conclusion, the present software system allowed rapid determination of the primary structures of AGP glycans. The fucosylated glycans as novel tumor markers have clinical relevance in the diagnosis and assessment of cancer progression as well as patient prognosis.
authors.affiliation: Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Asao
authors.forename: Shin
authors.initials: S
authors.lastname: Yazawa
authors.forename: Toyo
authors.initials: T
authors.lastname: Nishimura
authors.forename: Takashi
authors.initials: T
authors.lastname: Hayashi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Shimaoka
authors.forename: Abby R
authors.initials: AR
authors.lastname: Saniabadi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuwano
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood; D016022:Case-Control Studies; D002852:Chromatography, Ion Exchange; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005643:Fucose / Q000737:chemistry*; D006031:Glycosylation; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D009369:Neoplasms / Q000097:blood* / Q000175:diagnosis*; D009961:Orosomucoid / Q000032:analysis*; D010949:Plasma / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry; D011379:Prognosis; D012984:Software
chemical_list: D014408:Biomarkers, Tumor; D009961:Orosomucoid; D011134:Polysaccharides; D005643:Fucose