Delineating Diseases by IMS-MS Profiling of Serum N-linked Glycans

Altered branching and aberrant expression of N-linked glycans is known to be associated with disease states such as cancer. However, the complexity of determining such variations hinders the development of specific glycomic approaches for assessing disease states. Here, we examine a combination of i...

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Bibliographic Details
Published in:Journal of proteome research 2012-02, Vol.11 (2), p.576-585
Main Authors: Isailovic, Dragan, Plasencia, Manolo D, Gaye, Maissa M, Stokes, Sarah T, Kurulugama, Ruwan. T, Pungpapong, Vitara, Zhang, Min, Kyselova, Zuzana, Goldman, Radoslav, Mechref, Yehia, Novotny, Milos V, Clemmer, David E
Format: Article
Language:English
Subjects:
Adolescent
Adult
Computational Biology - methods
Glycoproteins - blood
Glycoproteins - chemistry
Humans
Liver Cirrhosis - blood
Liver Neoplasms - blood
Polysaccharides - blood
Polysaccharides - chemistry
Polysaccharides - classification
Principal Component Analysis
Spectrometry, Mass, Electrospray Ionization - methods
Statistics, Nonparametric
Tandem Mass Spectrometry
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Summary:Altered branching and aberrant expression of N-linked glycans is known to be associated with disease states such as cancer. However, the complexity of determining such variations hinders the development of specific glycomic approaches for assessing disease states. Here, we examine a combination of ion mobility spectrometry (IMS) and mass spectrometry (MS) measurements, with principal component analysis (PCA) for characterizing serum N-linked glycans from 81 individuals: 28 with cirrhosis of the liver, 25 with liver cancer, and 28 apparently healthy. Supervised PCA of combined ion-mobility profiles for several, to as many as 10 different mass-to-charge ratios for glycan ions, improves the delineation of diseased states. This extends an earlier study [J. Proteome Res. 2008, 7, 1109–1117] of isomers associated with a single glycan (S1H5N4) in which PCA analysis of the IMS profiles appeared to differentiate the liver cancer group from the other samples. Although performed on a limited number of test subjects, the combination of IMS-MS for different combinations of ions and multivariate PCA analysis shows promise for characterizing disease states.
ISSN:1535-3893
1535-3907
DOI:10.1021/pr200777u