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Precise structural analysis of O-linked oligosaccharides in human serum
Masahiko Yabu1, Hiroaki Korekane, Yasuhide Miyamoto
1Department of Immunology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-2 Nakamichi, Higashinari-ku, Osaka 537-8511, Japan.
Glycobiology
|March 26, 2014
Summary
This study established a reference database for O-glycans in healthy human sera, identifying 20 types and their structures. These findings aid in discovering novel carbohydrate tumor markers for early cancer detection.
Area of Science:
- Glycomics
- Biochemistry
- Cancer Biomarkers
Background:
- O-glycans, a type of carbohydrate structure, are recognized as potential biomarkers for cancer detection.
- Establishing a baseline profile of O-glycans in healthy individuals is crucial for identifying aberrant structures associated with tumors.
Purpose of the Study:
- To create a comprehensive reference database of O-glycan structures in healthy human sera.
- To identify and quantify O-glycans present in healthy serum to serve as a benchmark for tumor marker discovery.
Main Methods:
- Serum O-glycans were isolated using hydrazine treatment and fluorescently labeled with aminopyridine.
- Structures were elucidated through 2D mapping, enzymatic digestion, mass spectrometry (MS), and methanolysis.
- Quantification was performed, identifying glycans present at >0.01% of total O-glycans.
Main Results:
- A total of 20 O-glycans were identified: 18 acidic and 2 neutral.
- Major components included Neu5Acα2-3Galβ1-3GalNAc (61-64%) and Neu5Acα2-3Galβ1-3(Neu5Acα2-6)GalNAc (15-26%).
- Clinically relevant tumor markers like sialyl Tn antigen and sialyl Lewis X antigen were found at low levels (∼0.1-0.2%), while CA19-9 and DU-PAN-2 were below detection limits (<0.01%).
Conclusions:
- The detailed O-glycan profile of healthy human sera provides a critical reference database.
- This baseline data is essential for the identification and validation of novel O-glycan-based tumor markers.
- The study highlights the potential of O-glycans as sensitive and specific indicators for early cancer diagnosis.
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