Mass spectrometry in clinical glycomics: The path from biomarker identification to clinical implementation

Abstract

Over the past decades, the genome and proteome have been widely explored for biomarker discovery and personalized medicine. However, there is still a large need for improved diagnostics and stratification strategies for a wide range of diseases. Post-translational modification of proteins by glycosylation affects protein structure and function, and glycosylation has been implicated in many prevalent human diseases. Numerous proteins for which the plasma levels are nowadays evaluated in clinical practice are glycoproteins. While the glycosylation of these proteins often changes with disease, their glycosylation status is largely ignored in the clinical setting. Hence, the implementation of glycomic markers in the clinic is still in its infancy. This is for a large part caused by the high complexity of protein glycosylation itself and of the analytical techniques required for their robust quantification. Mass spectrometry-based workflows are particularly suitable for the quantification of glycans and glycoproteins, but still require advances for their transformation from a biomedical research setting to a clinical laboratory. In this review, we describe why and how glycomics is expected to find its role in clinical tests and the status of current mass spectrometry-based methods for clinical glycomics.

Developments and perspectives in high-throughput protein glycomics: enabling the analysis of thousands of samples

“…MS of intact proteins allows the analysis of glycosylation in a protein-specific way along with other protein structural features and PTMs. A big advantage of intact protein analysis is the often very simple sample preparation workflow, favoring the use of this approach in biopharma for batch release as well as in clinical diagnostics ( de Haan, Wuhrer et al. 2020 ).…”

Cracking the Breast Cancer Glyco-Code through Glycan-Lectin Interactions: Targeting Immunosuppressive Macrophages

“…This becomes even more complex for TNBC, which encompasses six distinct molecular subtypes, as described in Section 2 , and presents the highest diversity among patients [ 20 ]. The recent developments in MS for glycomics and glycoproteomics and in mass spectrometry imaging allowing to uncover molecular information of glycosylation changes should prove great technological advances to the definition of the BC glycomes [ 101 , 102 ]. Other emergent tools in glycomics, such as glycan microarrays offer powerful high-throughput and high-sensitive tools for studying glycan-lectin interactions [ 103 ] and for glycan ligand discovery from glycomes [ 104 , 105 ].…”

Systematic review: Glycomics as diagnostic markers for hepatocellular carcinoma

“…11,12 Serum glycomics (also denoted as N-glycomics), or the assessment of glycoprotein-specific glycan features in serum, seem to be a promising strategy for biomarker discovery in liver diseases due to the fact that the majority of N-glycans found in serum are attached to proteins produced by the liver. [12][13][14][15][16][17] A disturbance of the liver homeostasis leads to up-and downregulation of enzymes involved in the production of the N-glycan endproduct by the Golgi apparatus and endoplasmic reticulum of the hepatocytes. Thus, protein glycomic alterations in serum might reflect a disruption of liver function.…”