title: Abundance-ratio-based semiquantitative analysis of site-specific N-linked glycopeptides present in the plasma of hepatocellular carcinoma patients.
abstract: Aberrant structures of site-specific N-linked glycans are closely associated with the tumorigenesis of hepatocellular carcinoma (HCC), one of the most common fatal cancers worldwide. Vitronectin (VTN) is considered a candidate glycobiomarker of HCC. In this study, we describe a reliable and simple quantification strategy based on abundance ratios of site-specific N-linked glycopeptides of VTN to screen for potential biomarkers. A total of 14 unique N-linked glycans corresponding to 27 unique N-linked glycopeptides were characterized at three N-linked sites (Asn-86, -169, and -242) present in VTN. These glycans could be good candidate markers for HCC. Among these glycans, the abundance ratio of two representative glycoforms (fucosyl vs non-fucosyl) was significantly increased in HCC plasma relative to normal plasma. This strategy was also successfully applied to another potential HCC biomarker, haptoglobin. Furthermore, we demonstrate that our approach employing tandem mass tag (TMT) and target N-linked glycopeptides of VTN is a useful tool for quantifying specific glycans in HCC plasma relative to normal plasma. Our strategy represents a simple and potentially useful screening platform for the discovery of cancer-specific glycobiomarkers.
authors.affiliation: Yonsei Proteome Research Center and Department of Integrated OMICS for Biomedical Science, and Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University , Seoul 120-749, Korea.
authors.forename: Hyoung-Joo
authors.initials: HJ
authors.lastname: Lee
authors.forename: Hyun-Jeong
authors.initials: HJ
authors.lastname: Cha
authors.forename: Jong-Sun
authors.initials: JS
authors.lastname: Lim
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Si Young
authors.initials: SY
authors.lastname: Song
authors.forename: Hoguen
authors.initials: H
authors.lastname: Kim
authors.forename: William S
authors.initials: WS
authors.lastname: Hancock
authors.forename: Jong Shin
authors.initials: JS
authors.lastname: Yoo
authors.forename: Young-Ki
authors.initials: YK
authors.lastname: Paik
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001665:Binding Sites; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D002853:Chromatography, Liquid; D054794:Glycomics / Q000379:methods; D006020:Glycopeptides / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D011134:Polysaccharides / Q000097:blood / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry; D019096:Vitronectin / Q000097:blood / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D006020:Glycopeptides; D011134:Polysaccharides; D019096:Vitronectin