Biomarker Studies of Glycoproteins and Mass Spectrometry

Studying the status and features of proteins under different physiological conditions provides molecular signatures that have application in the diagnosis, prognosis, and pharmacological treatment of a given disease. Such clinically useful proteins are known as biomarkers. Glycoproteins are the post-translationally modified form of proteins that are abundant in the cellular milieu and therefore represent an important class of biomarkers in human. Several disorders including cancer, neurological disorders, inflammation, and degeneration have an association with aberrant glycosylation. Because glycosylation is a complex modification, the study of glycoproteins is challenging, especially in clinical samples where the sample type is complicated and the amount is often limited. Accurately identifying and quantifying abnormal glycoproteins in such scenarios requires a coordinated effort that relies on multiple methods. Mass spectrometry (MS) offers a precise one-point technique for studying complex proteins such as glycoproteins. Different ionization methods coupled with improved resolution and sensitivity of various MS instruments have boosted glycoprotein biomarker discovery in cardiovascular diseases, tropical diseases, and diseases such as cancer, diabetes, and more recently for COVID-19 diagnosis. This chapter summarizes various MS-based approaches for clinical glycoproteomics, their application in biomarker discovery in selected disease models, and challenges and opportunities related to clinical applications of the existing MS technologies.