Abstract
Modification of proteins by glycans plays a crucial role in mediating biological functions in both healthy and diseased states. Mass spectrometry (MS) has emerged as the most powerful tool for glycomic and glycoproteomic analyses advancing knowledge of many diseases. Such diseases include those of the pancreas which affect millions of people each year. In this review, recent advances in pancreatic disease research facilitated by MS-based glycomic and glycoproteomic studies will be examined with a focus on diabetes and pancreatic cancer. The last decade, and especially the last five years, has witnessed developments in both discovering new glycan or glycoprotein biomarkers and analyzing the links between glycans and disease pathology through MS-based studies. The strength of MS lies in the specificity and sensitivity of liquid chromatography-electrospray ionization MS for measuring a wide range of biomolecules from limited sample amounts from many sample types, greatly enhancing and accelerating the biomarker discovery process. Furthermore, imaging MS of glycans enabled by matrix-assisted laser desorption/ionization has proven useful in complementing histology and immunohistochemistry to monitor pancreatic disease progression. Advances in biological understanding and analytical techniques, as well as challenges and future directions for the field, will be discussed.
Highlights
Glycosylation and other post-translational modifications (PTMs) have been frequently studied in the context of diseases (Chen Z. et al, 2018; Shi et al, 2019; Zhang H. et al, 2020; Chen et al, 2021)
Carbohydrate antigen 19-9 (CA 19-9) and sialyl-TRA were stained and visualized using immunofluorescence. These two glycan markers were previously found to define separate subpopulations of pancreatic cancer cells (Barnett et al, 2017). These analyses identified in Pancreatic ductal adenocarcinoma (PDAC) tissues increased sialylation, poly-LacNAc extensions, branching, and fucosylation of high-mass glycans (Mcdowell et al, 2020)
The past five years have provided a rich body of work using MSbased analysis of glycans and glycoproteins to derive insights into pancreatic diseases
Summary
Glycosylation and other post-translational modifications (PTMs) have been frequently studied in the context of diseases (Chen Z. et al, 2018; Shi et al, 2019; Zhang H. et al, 2020; Chen et al, 2021). Recent studies have focused on the most abundant species in blood as targets for biomarker discovery, bypassing the need for enrichment of less concentrated species or depletion of the most concentrated These studies have investigated glycation of human serum albumin (HSA) as markers for diabetes to complement HbA1c (Korwar et al, 2015). We show the power of LC-MS in separating intact glycopeptides and fragmenting their constituent peptide backbones and glycans for confident identification and quantification This analysis identified markers of higher risk for T2D, including increasing branching at the second glycosite and decreased sialylation at the third glycosite (Keser et al, 2021). These studies illustrate the importance of protein glycosylation on cancer progression
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