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Plasma miRNAs as Biomarkers to Identify Patients with Castration-Resistant Metastatic Prostate Cancer
The Vancouver Prostate Centre, Vancouver General Hospital, Vancouver, BC V6H 3Z6, Canada
Departments of Experimental Therapeutics, Vancouver, BC V5Z 1L3, Canada
Departments of Medical Oncology, BC Cancer Agency, Vancouver, BC V5Z 4E6, Canada
Departments of Urologic Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada
Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, BC V5Z 4E3, Canada
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 16 February 2013; in revised form: 20 March 2013 / Accepted: 22 March 2013 / Published: 10 April 2013
Abstract: MicroRNAs (miRNAs) have emerged as key regulators of numerous biological processes, and increasing evidence suggests that circulating miRNAs may be useful biomarkers of clinical disease. In this study, we sought to identify plasma miRNAs that differentiate patients with metastatic castration resistant prostate cancer (mCRPC) from those with localized prostate cancer (PCa). Pooled plasma samples from patients with localized PCa or mCRPC (25 per group) were assayed using the Exiqon miRNA qPCR panel, and the differential expression of selected candidates was validated using qRT-PCR. We identified 63 miRNAs upregulated in mCRPC versus localized PCa, while only four were downregulated. Pearson’s correlation analysis revealed two highly correlated groups: one consisting of miR-141, miR375 and miR-200c and the other including miR151-3p, miR423-3p, miR-126, miR152 and miR-21. A third group, containing miR-16 and miR-205, showed less correlation. One miRNA from each group (miR-141, miR151-3p and miR-16) was used for logistic regression analysis and proved to increase the sensitivity of the prostate-specific antigen (PSA) test alone. While no miRNA alone differentiated localized PCa and mCRPC, combinations had greater sensitivity and specificity. The expression of these 10 candidates was assayed for association with clinical parameters of disease progression through the cBio portal. Our results demonstrate that plasma levels of selected miRNAs are potential biomarkers to differentiate localized PCa and mCRPC.
Keywords: microRNA; prostate cancer; metastasis; PSA; castration resistant
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Watahiki, A.; Macfarlane, R.J.; Gleave, M.E.; Crea, F.; Wang, Y.; Helgason, C.D.; Chi, K.N. Plasma miRNAs as Biomarkers to Identify Patients with Castration-Resistant Metastatic Prostate Cancer. Int. J. Mol. Sci. 2013, 14, 7757-7770.
Watahiki A, Macfarlane RJ, Gleave ME, Crea F, Wang Y, Helgason CD, Chi KN. Plasma miRNAs as Biomarkers to Identify Patients with Castration-Resistant Metastatic Prostate Cancer. International Journal of Molecular Sciences. 2013; 14(4):7757-7770.
Watahiki, Akira; Macfarlane, Robyn J.; Gleave, Martin E.; Crea, Francesco; Wang, Yuzhuo; Helgason, Cheryl D.; Chi, Kim N. 2013. "Plasma miRNAs as Biomarkers to Identify Patients with Castration-Resistant Metastatic Prostate Cancer." Int. J. Mol. Sci. 14, no. 4: 7757-7770.