Abstract
Aberrant and dysregulated protein glycosylation is a well-established event in the process of oncogenesis and cancer progression. Years of study on the glycobiology of cancer have been focused on the development of clinically viable diagnostic applications of this knowledge. However, for a number of reasons, there has been only sparse and varied success. The causes of this range from technical to biological issues that arise when studying protein glycosylation and attempting to apply it to practical applications. This review focuses on the pitfalls, advances, and future directions to be taken in the development of clinically applicable quantitative assays using glycan moieties from serum-based proteins as analytes. Topics covered include the development and progress of applications of lectins, mass spectrometry, and other technologies towards this purpose. Slowly but surely, novel applications of established and development of new technologies will eventually provide us with the tools to reach the ultimate goal of quantification of the full scope of heterogeneity associated with the glycosylation of biomarker candidate glycoproteins in a clinically applicable fashion.
Highlights
Aberrant and dysregulated protein glycosylation is a well-established event in the process of oncogenesis and cancer progression
Great advances have been made with approaches using immunoaffinity enrichment of peptides or proteins followed by MRM/ SRM-based quantification, achieving levels of sensitivity applicable to the concentration range at which low-abundance tumor biomarkers are found [95,96,97,98,99]. This type of methodology has been used in combination with different types of glycan affinity enrichment strategies, thereby producing hybrid assays in which classic glycoprotein enrichment strategies are used for capture of specific glycoforms, and mass spectrometry (MS) is used for detection and quantification of the protein in those subpopulations by monitoring the MS2 fragmentation of non-glycosylated tryptic peptides
When the recent literature is searched for ‘glycosylation quantification’, it quickly becomes obvious that MS-based approaches have almost become an absolute requirement
Summary
Aberrant and dysregulated protein glycosylation is a well-established event in the process of oncogenesis and cancer progression. Another approach involves the detection and quantification of a particular glycan structure shown to be associated with cancer, such as the antibody-based measurement of the blood group antigen Lewisa in the CA19-9 assay [42].
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