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Abundance-Ratio-Based Semiquantitative Analysis of Site-Specific N-Linked Glycopeptides Present in the Plasma of Hepatocellular Carcinoma Patients

Authors
 Hyoung-Joo Lee  ;  Hyun-Jeong Cha  ;  Jong-Sun Lim  ;  Sun Hee Lee  ;  Si Young Song  ;  Hoguen Kim  ;  William S. Hancock  ;  Jong Shin Yoo  ;  Young-Ki Paik 
Citation
 JOURNAL OF PROTEOME RESEARCH, Vol.13(5) : 2328-2338, 2014 
Journal Title
 JOURNAL OF PROTEOME RESEARCH 
ISSN
 1535-3893 
Issue Date
2014
MeSH
Adult ; Aged ; Amino Acid Sequence ; Binding Sites ; Biomarkers, Tumor/blood ; Biomarkers, Tumor/metabolism ; Carcinoma, Hepatocellular/blood ; Carcinoma, Hepatocellular/metabolism* ; Carcinoma, Hepatocellular/pathology ; Chromatography, Liquid ; Glycomics/methods ; Glycopeptides/blood ; Glycopeptides/chemistry ; Glycopeptides/metabolism* ; Humans ; Liver Neoplasms/blood ; Liver Neoplasms/metabolism* ; Liver Neoplasms/pathology ; Male ; Middle Aged ; Molecular Sequence Data ; Neoplasm Staging ; Polysaccharides/blood ; Polysaccharides/metabolism* ; Proteomics/methods ; Reproducibility of Results ; Tandem Mass Spectrometry ; Vitronectin/blood ; Vitronectin/metabolism
Keywords
haptoglobin ; HCC ; N-linked glycopeptides ; quantification ; TMT ; vitronectin
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.
Full Text
http://pubs.acs.org/doi/abs/10.1021/pr4011519
DOI
10.1021/pr4011519
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hogeun(김호근)
Song, Si Young(송시영) ORCID logo https://orcid.org/0000-0002-1417-4314
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/99015
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