Unravelling the sugar-coating of prostate-specific antigen : method development and its application to prostate cancer research

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Unravelling the sugar-coating of prostate-specific antigen : method development and its application to prostate cancer research

Type: Doctoral Thesis
Title: Unravelling the sugar-coating of prostate-specific antigen : method development and its application to prostate cancer research
Author: Kammeijer, G.S.M.
Issue Date: 2019-03-07
Keywords: Prostate Cancer
Prostate-Specific Antigen
Glycosylation
Glycans
Glycomics
Glycopeptides
Glycoproteomics
CE-ESI-MS
Capillary Electrophoresis-Electrospray Ionization-Mass Spectrometry
Abstract: The aim of this thesis is to explore the glycosylation of PSA as well as to study if alterations can be observed between patients with indolent and malignant PCa. For this purpose the powerful analytical platform CE-ESI-MS(/MS) was explored with a special focus on the analysis of glycans and glycopeptides (Chapter 1). The first section of the thesis describes the different method developments implemented for the analysis of PSA with CE-ESI-MS. Namely, Chapter 2 describes that CE-ESI-MS enables to separate glycopeptides with differently linked sialic acids without any additional sample treatment, Chapter 3 shows that an introduction of a dopant enriched nitrogen gas improves the limit of detection (sensitivity) of glycopeptides and Chapter 4 introduces a novel labeling procedure of total plasma N-glycome with the hydrazide Girard’s reagent P. Chapter 5 describes the development of a PSA Glycomics Assay which allows the capture of intact PSA from patients’ urine followed by analysis with the optimized CE-ESI-MS platform (Chapters 2 and 3). Finally, Chapter 6 offers a general discussion about future developments, the potential of PSA glycosylation in the clinical setting, showing the relevance of our results and how these may contribute to further clinical applications towards personalized medicine.
Promotor: Supervisor: Wuhrer M. Co-Supervisor: Reijke M. de
Faculty: Faculty of Medicine, Leiden University Medical Center (LUMC)
University: Leiden University
Uri: urn:isbn:9789463802499
Handle: http://hdl.handle.net/1887/69482
 

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