Proteomic Identification and Systematic Verification of Biomarkers for Aggressive Prostate Cancer
Year: 2015
Type: dissertation
Study design: Observational Study
Abstract: Despite prostate cancer’s status as the most common cancer to affect men in the Western world, only an estimated 20% of men will die from it. Due to the lack of effective means of prognostication, many men are unnecessarily biopsied and treated. The early and non-invasive identification of lethal disease would have a profound impact on the current practice of prostate cancer management. To this end, the work presented in this thesis describes efforts to characterize proteins in a prostatic fluid known as expressed prostatic secretions (EPS), and to delineate factors in this fluid that demonstrate a high potential as prognostic biomarkers. Using different mass spectrometry-based platforms, I present both a global view of the EPS proteome, as well as targeted, quantitative measures of promising biomarker candidates in this fluid. In order to generate an archive of soluble and secreted factors present in the proteome of EPS, I used shotgun proteomics to analyze direct-EPS and EPS-urine. This led to the identification of over 2000 proteins that comprise the EPS proteome. The data was integrated with other publicly accessible information, such as gene expression profiles and immunohistochemistry images, to characterize this proteome. Furthermore, a collection of prostate-enriched proteins was identified by comparing the proteomes of EPS-urine and urine, demonstrating the unique protein profile of EPS. Next, comparative proteomic profiling of direct-EPS from organ confined and extracapsular tumors produced a long list of potential biomarker candidates. A targeted assay was systematically developed in order to quantitatively assess the performance of the most promising candidates in cohorts of EPS-urines from a heterogeneous population of prostate cancer patients and controls. Utilizing the assay, a number of candidates were verified to be putative biomarkers for prostate cancer diagnosis and prognosis. This information needs to be further validated and holds promise for improved prostate cancer management.
Source: TSpace (University of Toronto)
Author: Yunee Kim
Language: English
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W2620836150