Precise structural analysis of O-linked oligosaccharides in human serum.
Glycobiology
; 24(6): 542-53, 2014 Jun.
Article
em En
| MEDLINE
| ID: mdl-24663386
ABSTRACT
O-glycans are suitable targets as novel and useful tumor markers. The structures of O-glycans in human sera from four healthy controls were precisely analyzed to obtain the reference O-glycan database. O-glycans were prepared from sera by hydrazine treatment followed by fluorescent labeling with aminopyridine and identified using two-dimensional mapping, enzymatic digestion and mass spectrometry (MS) together with methanolysis and the use of newly synthesized sulfated oligosaccharides as standards. O-glycans, present at more than 0.01% of the total O-glycans, were analyzed, and 18 kinds of acidic and 2 kinds of neutral glycans were identified. NeuAcα2-3Galß1-3N-acetylgalactosamine (GalNAc) (61-64%), NeuAcα2-3Galß1-3(NeuAcα2-6)GalNAc (15-26%) and Galß1-3GalNAc (6-14%) were major components while other sialylated glycans, Galß1-3(NeuAcα2-6)GalNAc, Galß1-4GlcNAcß1-6(NeuAcα2-3Galß1-3)GalNAc and NeuAcα2-3Galß1-4GlcNAcß1-6(NeuAcα2-3Galß1-3)GalNAc were relatively minor components, accounting for â¼1-2%. Very minor glycans accounting for â¼0.01-0.1% of the total include (i) the neutral glycan, Galß1-4GlcNAcß1-6(Galß1-3)GalNAc, (ii) sialylated glycans, having sialyl Tn antigen, agalacto and trisialylated structures, (iii) fucosylated glycans forming blood type H antigen, blood type A antigen, blood type B antigen, Lewis X antigen and sialyl Lewis X antigen and (iv) sulfated glycans, having 6-sulfo and 3'-sulfo structures. Two kinds of clinically applied tumor markers namely sialyl Tn antigen and sialyl Lewis X antigen in healthy controls sera were revealed to be present at â¼0.1-0.2% of the total. However, other markers such as CA19-9 and DU-PAN-2 were not found, suggesting the relative amounts of these glycans to be <0.01%. These detailed O-glycan profiles will help to find novel carbohydrate tumor markers.
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MEDLINE
Assunto principal:
Oligossacarídeos
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Polissacarídeos
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Biomarcadores Tumorais
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Neoplasias
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article