Glycan Biomarker Discovery
Version of Record online: 9 OCT 2013
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PROTEOMICS - Clinical Applications
Special Issue: Glycan Biomarker Discovery
Volume 7, Issue 9-10, pages 595–596, October 2013
How to Cite
Pierce, M. and Taniguchi, N. (2013), Glycan Biomarker Discovery. Prot. Clin. Appl., 7: 595–596. doi: 10.1002/prca.201370054
- Issue online: 9 OCT 2013
- Version of Record online: 9 OCT 2013
The most complex post-translational modification of proteins, glycosylation, is controlled by diverse regulatory mechanisms that include the 3D structure of the protein, the complement of glycosyltransferases and glycosidases that are expressed, the transport of substrates into the endoplasmic reticulum and the Golgi, and the topographical transit of the proteins through these compartments during biosynthesis. It is not surprising, therefore, that the glycans expressed on a particular protein reflect the state of the cell that has synthesized it, be it normalcy or that of pathology. Difficulties in our ability to focus on protein glycosylation as a means to develop diagnostic and prognostic assays for particular disorders and diseases are beginning to be overcome, however, as Glycomic technologies are developed. The collection of studies published in this issue demonstrates progress in developing several tools and methodologies to analyze tissues and fluids for altered protein glycosylation, as well as for identifying particular protein glycosylation markers that are associated with the disease state.
The first three contributions are largely focused on describing state-of-the-art technologies and reagents to perform glycoproteomics and identify potential biomarkers. The first, from G. Hart's laboratory , summarizes current glycoproteomics and mass spectrometric approaches to identify site-specific glycosylation with the monosaccharide O-GlcNAc. This post-translational modification is as ubiquitous and its functions as diverse as phosphorylation, and there are indications that it may be able to identify the pre-diabetic state. Next, K. Ueda presents an overview of strategies for identification of potential cancer glycan markers using glycoproteomic strategies . R. Cummings’ laboratory  then presents a comprehensive review of the utility of the Tn and sialyl-Tn antigens in identifying various cancers and other diseases and disorders, such as IgA nephropathy, concentrating on the mechanism that causes loss of the T-synthase and production of these antigens, namely, mutations in the molecular chaperone, Cosmc.
The next three papers describe progress using lectin-based analyses to discover novel biomarkers. B. Haab's laboratory  discusses a novel methodology to predict O-glycan motifs by analyzing the binding of multi-lectins to the Consortium for Functional Glycomics glycan array, and applying this method to identify and distinguish motifs on MUC1 synthesized and secreted by eight cultured pancreatic cancer cell lines. Narimatsu's laboratory  discusses a lectin/antibody-based assay to quantify a specific glycoform of Mac-2 binding protein (galectin-3) in serum as a marker for liver fibrosis. Next, Miyoshi's laboratory  has developed an assay for serum Mac-2 binding protein that can assist diagnosis of nonalcoholic fatty liver disease and, predicting severity of this disease and distinguishing between this disease and simple steatosis.
The final four contributions describe somewhat more advanced glycan markers for particular diseases. Kitazume and Taniguchi, et al.  describe a glycoform of amyloid b peptide secreted by vascular endothelial cells that is O-glycosylated. This glycoform has the potential to be a biomarker for acute coronary syndrome. Miyamoto and Lebrilla  have evaluated to protein enrichment techniques to evaluate glycan differences in serum and on IgG to demonstrate differences in serum from non-diseased and lung cancer patients. Drake's laboratory  has developed glycoproteomic methods to analyze expressed prostatic secretions on total glycoproteins and prostatic acid phosphatase and showed an association of an increase in bisected N-linked glycans, and loss of highly branched N-linked glycans, with prostatic carcinoma severity. Finally, Mehta and colleagues  demonstrated that N-linked glycan analysis of total serum glycoproteins could distinguish well hepatocellular carcinoma from cirrhosis. When combined with alpha-fetoprotein levels, the sensitivity of the method increased to 95% with a specificity of 90%, which is very impressive.
It is clear from these contributions that significant progress has been made in the identification of glycan biomarkers for several diseases, as well as development of assays to quantify them. These diseases and disorders range from hepatocellular and epithelial cancers, to acute coronary syndrome, prediabetes, and various liver diseases. There is no doubt that as advances in glycomic technologies and assays continue to be developed, we will soon be able to see past the tip of the “iceberg”, where we are now, and dive deep into the treasure of glycobiomarkers with clinical applications that we will assuredly discover.