Glycomic profiling of targeted serum haptoglobin for gastric cancer using nano LC/MS and LC/MS/MS

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Gastric cancer has one of the highest cancer mortality rates worldwide, largely because of difficulties in early-stage detection. Aberrant glycosylation in serum proteins is associated with many human diseases including inflammation and various types of cancer. Serum-based global glycan profiling using mass spectrometry has been explored and has already led to several potential glycan markers for several disease states. However, localization of the aberrant glycosylation is desirable in order to improve the specificity and sensitivity for clinical use. Here, we combined protein-specific immunoaffinity purification, glycan release, and MS analysis to examine haptoglobin glycosylation of gastric cancer patients for glyco-markers. Age-and sex-matched 60 serum samples (30 cancer patients and 30 healthy controls) were used to profile and quantify haptoglobin N-glycans. A T-test based statistical analysis was performed to identify potential glyco-markers for gastric cancer. Interestingly, abundances of several tri-and tetra-antennary fucosylated N-glycans were increased in gastric cancer patients. Additionally, structural analysis via LC/MS/MS indicated that the fucosylated complex type N-glycans were primarily decorated with antenna fucose, which can be categorized as sialyl-Lea or sialyl-Lex type structures. This platform demonstrates quantitative, structure-specific profiling of haptoglobin glycosylation for the purposes of biomarker discovery for gastric cancer.
Publisher
ROYAL SOC CHEMISTRY
Issue Date
2016-09
Language
English
Article Type
Article
Keywords

REACTIVE ALPHA-FETOPROTEIN; N-GLYCOSYLATION STATUS; HEPATOCELLULAR-CARCINOMA; PANCREATIC-CANCER; PROTEIN GLYCOSYLATION; BETA-HAPTOGLOBIN; COLON-CANCER; FUCOSYLATED HAPTOGLOBIN; BREAST-CANCER; EXPRESSION

Citation

MOLECULAR BIOSYSTEMS, v.12, no.12, pp.3611 - 3621

ISSN
1742-206X
DOI
10.1039/c6mb00559d
URI
http://hdl.handle.net/10203/219667
Appears in Collection
BS-Journal Papers(저널논문)
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