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Title: Utilisation of mass spectrometry in the quest for male urogenital cancer biomarkers
Author: Flatley, Brian
Awarding Body: University of Reading
Current Institution: University of Reading
Date of Award: 2013
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This thesis presents the application of mass spectrometry to the field of biomarker discovery. It focuses on the identification of diagnostic and prognostic protein biomarkers for prostate and penile cancer respectively. Matrix-assisted laser desorption/ionisation (MALDI) and electro spray ionisation (ESI) are key ionisation techniques used in mass spectrometry for the analysis of macromolecules such as proteins. High-throughput MALDI mass spectrometry profiling was used to analyse urine and plasma samples from men attending a urology clinic for confirmation of their prostate disease status. The results of the MALDI MS profiling found that the abundance of p-microseminoprotein (MSMB) when measured in urine taken following a digital rectal examination of the prostate gland was lower in men with prostate cancer over men that were diagnosed with benign prostate conditions. MALDI MS was also used to map the spatial distribution of biomolecules in penile tissue slices that contained invasive squamous epithelial cell carcinoma and areas of benign epithelial cells. The results of this mapping highlighted a number of mass-to-charge (mlz) ratios where the abundance of the underlying biomolecule was significantly different in one region when compared to the other. One difference at mlz 11,637 was suggested to represent the calcium binding protein family member SIOOA4. The levels of this protein were measured in a larger sample cohort using immunohistochemistry, where it was found that the number of epithelial cells in malignant penile tissue that were positive for SlOOA4 could be correlated to the clinical grade assigned to that tumour.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available