Discovery of novel potential protein diagnostic biomarkers for prostate cancer in serum and tears

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Copyright: You, Jingjing
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Abstract
Prostate cancer (CaP) is a heterogeneous multifocal cancer with high prevalence worldwide, particularly in developed countries. The introduction of the prostate specific antigen (PSA) blood test for CaP diagnosis saw a dramatic increase in the reported incidence rate of CaP, but only a slight decrease in mortality, highlighting the importance of developing a more accurate CaP diagnostic test. Discovery of novel biomarkers has been the focus of cancer diagnostic research, with protein biomarkers of particular relevance due to their direct reflection of phenotype changes, resulting from pathophysiological conditions and their presence in the easy accessible body fluids. The aim of this PhD project was to detect, identify and verify potential novel CaP specific protein biomarkers that could distinguish CaP from benign prostatic hyperplasia (BPH) and healthy control groups; ideally identifying novel molecules that have the potential to improve the screening accuracy of the current CaP diagnostic test. Serum and tears were used as the sources of biomarkers in this study. As a circulatory body fluid, serum can reflect the molecular changes due to the presence of CaP. The tear film is of particular interest in CaP research, as both the prostate gland and the major tear producing gland, the lacrimal gland, are androgen regulated. Various proteomic approaches including gel based, mass spectrometry based and targeted antibody based techniques were used in this study to examine the serum and tear proteomes as well as for protein identification and quantitation. The key finding of the present study was the identification of five serum proteins (albumin, fetuin A, IGHM, hemopexin and C4BPA) and one peptide (VPSHAVVAR) derived from the tear protein, lactoferrin, as potential biomarkers for CaP. From these proteins, albumin and fetuin A were evaluated in a separate small sample group of subjects, with these results further indicating their potential for differentiating between CaP and control groups. Moreover, this was also the first study which has used MRM to validate presence of a novel tear protein dermcidin, to relatively quantify six tear proteins and to detect a potential CaP biomarker peptide in tears. The findings from this study suggest that, using larger sample size to verify the results presented, the development of more accurate and non-invasive clinical tests for the diagnosis of CaP may be possible.
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Author(s)
You, Jingjing
Supervisor(s)
Li, Yong
Willcox, Mark
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Publication Year
2011
Resource Type
Thesis
Degree Type
PhD Doctorate
UNSW Faculty
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