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Detection of Aberrant Glycosylation of Serum Haptoglobin for Gastric Cancer Diagnosis Using a Middle-Up-Down Glycoproteome Platform

Authors
 Seunghyup Jeong  ;  Unyong Kim  ;  Myungjin Oh  ;  Jihyeon Nam  ;  Sehoon Park  ;  Yoonjin Choi  ;  Dongho Lee  ;  Jaehan Kim  ;  Hyunjoo An 
Citation
 JOURNAL OF PERSONALIZED MEDICINE, Vol.11(6) : 575, 2021-06 
Journal Title
JOURNAL OF PERSONALIZED MEDICINE
Issue Date
2021-06
Keywords
biomarker ; gastric cancer ; glycopeptide ; haptoglobin ; mass spectrometry ; middle-up-down
Abstract
Gastric cancer is a frequently occurring cancer and is the leading cause of cancer-related deaths. Recent studies have shown that aberrant glycosylation of serum haptoglobin is closely related to gastric cancer and has enormous potential for use in diagnosis. However, there is no platform with high reliability and high reproducibility to comprehensively analyze haptoglobin glycosylation covering microheterogeneity to macroheterogeneity for clinical applications. In this study, we developed a middle-up-down glycoproteome platform for fast and accurate monitoring of haptoglobin glycosylation. This platform utilizes an online purification of LC for sample desalting, and an in silico haptoglobin glycopeptide library constructed by combining peptides and N-glycans to readily identify glycopeptides. In addition, site-specific glycosylation with glycan heterogeneity can be obtained through only a single MS analysis. Haptoglobin glycosylation in clinical samples consisting of healthy controls (n = 47) and gastric cancer patients (n = 43) was extensively investigated using three groups of tryptic glycopeptides: GP1 (including Asn184), GP2 (including Asn207 and Asn211), and GP3 (including Asn241). A total of 23 individual glycopeptides were determined as potential biomarkers (p < 0.00001). In addition, to improve diagnostic efficacy, we derived representative group biomarkers with high AUC values (0.929 to 0.977) through logistic regression analysis for each GP group. It has been found that glycosylation of haptoglobin is highly associated with gastric cancer, especially the glycosite Asn241. Our assay not only allows to quickly and easily obtain information on glycosylation heterogeneity of a target glycoprotein but also makes it an efficient tool for biomarker discovery and clinical diagnosis.
DOI
10.3390/jpm11060575
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Choi, Yoon Jin(최윤진)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/190894
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