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Circulating miRNAs as non-invasive biomarkers to predict aggressive prostate cancer after radical prostatectomy

BACKGROUND: Prostate cancer is an extremely heterogeneous disease. Despite being clinically similar, some tumours are more likely to recur after surgery compared to others. Distinguishing those that need adjuvant or salvage radiotherapy will improve patient outcomes. The goal of this study was to id...

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Autores principales: Hoey, C., Ahmed, M., Fotouhi Ghiam, A., Vesprini, D., Huang, X., Commisso, K., Commisso, A., Ray, J., Fokas, E., Loblaw, D. A., He, H. H., Liu, S. K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533745/
https://www.ncbi.nlm.nih.gov/pubmed/31122242
http://dx.doi.org/10.1186/s12967-019-1920-5
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author Hoey, C.
Ahmed, M.
Fotouhi Ghiam, A.
Vesprini, D.
Huang, X.
Commisso, K.
Commisso, A.
Ray, J.
Fokas, E.
Loblaw, D. A.
He, H. H.
Liu, S. K.
author_facet Hoey, C.
Ahmed, M.
Fotouhi Ghiam, A.
Vesprini, D.
Huang, X.
Commisso, K.
Commisso, A.
Ray, J.
Fokas, E.
Loblaw, D. A.
He, H. H.
Liu, S. K.
author_sort Hoey, C.
collection PubMed
description BACKGROUND: Prostate cancer is an extremely heterogeneous disease. Despite being clinically similar, some tumours are more likely to recur after surgery compared to others. Distinguishing those that need adjuvant or salvage radiotherapy will improve patient outcomes. The goal of this study was to identify circulating microRNA that could independently predict prostate cancer patient risk stratification after radical prostatectomy. METHODS: Seventy-eight prostate cancer patients were recruited at the Odette Cancer Centre in Sunnybrook Health Sciences Centre. All patients had previously undergone radical prostatectomy. Blood samples were collected simultaneously for PSA testing and miRNA analysis using NanoString nCounter technology. Of the 78 samples, 75 had acceptable miRNA quantity and quality. Patients were stratified into high- and low-risk categories based on Gleason score, pathological T stage, surgical margin status, and diagnostic PSA: patients with Gleason ≥ 8; pT3a and positive margin; pT3b and any margin; or diagnostic PSA > 20 µg/mL were classified as high-risk (n = 44) and all other patients were classified as low-risk (n = 31). RESULTS: Using our patient dataset, we identified a four-miRNA signature (miR-17, miR-20a, miR-20b, miR-106a) that can distinguish high- and low-risk patients, in addition to their pathological tumour stage. High expression of these miRNAs is associated with shorter time to biochemical recurrence in the TCGA dataset. These miRNAs confer an aggressive phenotype upon overexpression in vitro. CONCLUSIONS: This proof-of-principle report highlights the potential of circulating miRNAs to independently predict risk stratification of prostate cancer patients after radical prostatectomy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-019-1920-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-65337452019-05-28 Circulating miRNAs as non-invasive biomarkers to predict aggressive prostate cancer after radical prostatectomy Hoey, C. Ahmed, M. Fotouhi Ghiam, A. Vesprini, D. Huang, X. Commisso, K. Commisso, A. Ray, J. Fokas, E. Loblaw, D. A. He, H. H. Liu, S. K. J Transl Med Research BACKGROUND: Prostate cancer is an extremely heterogeneous disease. Despite being clinically similar, some tumours are more likely to recur after surgery compared to others. Distinguishing those that need adjuvant or salvage radiotherapy will improve patient outcomes. The goal of this study was to identify circulating microRNA that could independently predict prostate cancer patient risk stratification after radical prostatectomy. METHODS: Seventy-eight prostate cancer patients were recruited at the Odette Cancer Centre in Sunnybrook Health Sciences Centre. All patients had previously undergone radical prostatectomy. Blood samples were collected simultaneously for PSA testing and miRNA analysis using NanoString nCounter technology. Of the 78 samples, 75 had acceptable miRNA quantity and quality. Patients were stratified into high- and low-risk categories based on Gleason score, pathological T stage, surgical margin status, and diagnostic PSA: patients with Gleason ≥ 8; pT3a and positive margin; pT3b and any margin; or diagnostic PSA > 20 µg/mL were classified as high-risk (n = 44) and all other patients were classified as low-risk (n = 31). RESULTS: Using our patient dataset, we identified a four-miRNA signature (miR-17, miR-20a, miR-20b, miR-106a) that can distinguish high- and low-risk patients, in addition to their pathological tumour stage. High expression of these miRNAs is associated with shorter time to biochemical recurrence in the TCGA dataset. These miRNAs confer an aggressive phenotype upon overexpression in vitro. CONCLUSIONS: This proof-of-principle report highlights the potential of circulating miRNAs to independently predict risk stratification of prostate cancer patients after radical prostatectomy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-019-1920-5) contains supplementary material, which is available to authorized users. BioMed Central 2019-05-23 /pmc/articles/PMC6533745/ /pubmed/31122242 http://dx.doi.org/10.1186/s12967-019-1920-5 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Hoey, C.
Ahmed, M.
Fotouhi Ghiam, A.
Vesprini, D.
Huang, X.
Commisso, K.
Commisso, A.
Ray, J.
Fokas, E.
Loblaw, D. A.
He, H. H.
Liu, S. K.
Circulating miRNAs as non-invasive biomarkers to predict aggressive prostate cancer after radical prostatectomy
title Circulating miRNAs as non-invasive biomarkers to predict aggressive prostate cancer after radical prostatectomy
title_full Circulating miRNAs as non-invasive biomarkers to predict aggressive prostate cancer after radical prostatectomy
title_fullStr Circulating miRNAs as non-invasive biomarkers to predict aggressive prostate cancer after radical prostatectomy
title_full_unstemmed Circulating miRNAs as non-invasive biomarkers to predict aggressive prostate cancer after radical prostatectomy
title_short Circulating miRNAs as non-invasive biomarkers to predict aggressive prostate cancer after radical prostatectomy
title_sort circulating mirnas as non-invasive biomarkers to predict aggressive prostate cancer after radical prostatectomy
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533745/
https://www.ncbi.nlm.nih.gov/pubmed/31122242
http://dx.doi.org/10.1186/s12967-019-1920-5
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