Recent Advances in Mass Spectrometry-Based Glycomic and Glycoproteomic Studies of Pancreatic Diseases

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.

Characterization of Mesothelin Glycosylation in Pancreatic Cancer: Decreased Core Fucosylated Glycoforms in Pancreatic Cancer Patients’ Sera

“…These results emphasize the need for further studies evaluating Cf-MSLN in a larger cohort of patients, and including sera from other types of cancers in order to evaluate its specificity for PaC. Altogether, they show the importance of focusing on specific protein glycoforms altered in cancer, as well as exploring new glycoproteomic strategies [ 86 , 87 ] to high-throughput the analysis of Cf-MSLN and validate it as a PaC biomarker.…”

Cancer glycomics offers potential biomarkers and therapeutic targets in the framework of 3P medicine

“…Analysis of glycan structure requires the release of glycans. N -glycans are released from glycopeptides by peptide- N -glycosidase F (PNGase F) digestion ( 61 ). O -glycans have many core structures, and no general release enzymes are used; however, there are corresponding enzymes for specific core structures.…”

“…O -glycans have many core structures, and no general release enzymes are used; however, there are corresponding enzymes for specific core structures. Alternatively, any O -glycans can be released through the chemical process of β-elimination, with the potential for undesirable side effects ( 61 ). In recent years, bottom-up MS has been widely used to study glycosylation changes in tumorigenesis and development at different specificity levels including global, cell-specific, and local-specific.…”

Application of Mass Spectrometry in Pancreatic Cancer Translational Research

“…One study identified the modulated pathways of PCSCs via iTRAQ-based proteomic analysis, revealing that PCSCs changed proteomic and metabolite profiling compared to Panc1 parental cells. FAs and mevalonate play pivotal roles in the survival of PCSCs ( 42 ). Another study used LC-MS/MS to examine the protein modulation and lipid modulations in four PCSCs ( 43 ).…”