The potential of exosomal RNAs as biomarkers for prostate cancer

Brennan, Samuel Edward

The potential of exosomal RNAs as biomarkers for prostate cancer

Brennan, Samuel Edward

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Publication Type:: Thesis
Issue Date:: 2018

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Field	Value	Language
dc.contributor.author	Brennan, Samuel Edward
dc.date.accessioned	2018-06-19T03:50:24Z
dc.date.available	2020-05-25T19:21:48Z
dc.date.issued	2018
dc.identifier.uri	http://hdl.handle.net/10453/125510
dc.description	University of Technology Sydney. Faculty of Science.	en_AU
dc.description.abstract	Prostate cancer (PCa) is currently the most diagnosed cancer of Australian men, and the incidence is likely to keep increasing given our ageing population. Compounding this issue is the fact that the available tests are either discouragingly invasive, or lacking in specificity/sensitivity and offer no prognostic information. To overcome these issues we have been profiling the RNA content of exosomes isolated from PCa cell lines and patient body fluid samples including urine, plasma and saliva and have developed a miRNA signature for the diagnosis of early PCa. The large bodies of data also afforded an opportunity to probe the functional potential of exosomal RNAs. This was done using in silico methodologies as well as some experiments regarding the role of PCa exosomal RNAs in the tumour microenvironment. Urine exosomal miRNAs (exomiRs) provided the most robust diagnostic signature found during this project. They also hold some potential as prognostic and treatment response markers for PCa. Furthermore, urinary exomiRs can be harvested from patients in a non-invasive manner which is a significant step forward in the clinical care of PCa. The expression profile of urine exomiRs will be investigated in future experiments on much larger sample sizes to confirm the diagnostic and prognostic potential highlighted by this project. ExomiRs may also have roles in PCa immune evasion with the potential to inhibit the tumour killing and proliferative abilities of cells within the immune system, most likely natural killer cells and dendritic cells. This work needs further biological validation in future experiments. PCa exosomes were also shown to be potent inducers of myofibroblast transdifferentiation which suggests that PCa exosomes are in part responsible for metastatic progression of the disease. However, PCa exomiRs do not appear to be absorbed by recipient cells and do not impact the process of myofibroblast transdifferentiation.	en_AU
dc.format	Thesis (PhD)
dc.language.iso	en_AU	en_AU
dc.relation	https://opus.lib.uts.edu.au/bitstream/10453/125510/7/02whole.pdf
dc.rights	The author owns the copyright in this thesis including all reproduction and reuse rights for the work. The work may not be altered without the permission of the copyright owner. Attribution is essential when quoting or paraphrasing from this thesis.
dc.rights	au.edu.uts.lib/ppc
dc.rights	info:eu-repo/semantics/openAccess
dc.title	The potential of exosomal RNAs as biomarkers for prostate cancer	en_AU
dc.type	Thesis	en_AU
utslib.copyright.status	open_access

Abstract:

Prostate cancer (PCa) is currently the most diagnosed cancer of Australian men, and the incidence is likely to keep increasing given our ageing population. Compounding this issue is the fact that the available tests are either discouragingly invasive, or lacking in specificity/sensitivity and offer no prognostic information. To overcome these issues we have been profiling the RNA content of exosomes isolated from PCa cell lines and patient body fluid samples including urine, plasma and saliva and have developed a miRNA signature for the diagnosis of early PCa. The large bodies of data also afforded an opportunity to probe the functional potential of exosomal RNAs. This was done using in silico methodologies as well as some experiments regarding the role of PCa exosomal RNAs in the tumour microenvironment. Urine exosomal miRNAs (exomiRs) provided the most robust diagnostic signature found during this project. They also hold some potential as prognostic and treatment response markers for PCa. Furthermore, urinary exomiRs can be harvested from patients in a non-invasive manner which is a significant step forward in the clinical care of PCa. The expression profile of urine exomiRs will be investigated in future experiments on much larger sample sizes to confirm the diagnostic and prognostic potential highlighted by this project. ExomiRs may also have roles in PCa immune evasion with the potential to inhibit the tumour killing and proliferative abilities of cells within the immune system, most likely natural killer cells and dendritic cells. This work needs further biological validation in future experiments. PCa exosomes were also shown to be potent inducers of myofibroblast transdifferentiation which suggests that PCa exosomes are in part responsible for metastatic progression of the disease. However, PCa exomiRs do not appear to be absorbed by recipient cells and do not impact the process of myofibroblast transdifferentiation.

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http://hdl.handle.net/10453/125510