Urinary biomarkers for the detection of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia

Introduction: high-grade prostatic intraepithelial neoplasia (HGPIN) is a recognized precursor stage of PCa. Men who present HGPIN in a first prostate biopsy face years of active surveillance including repeat biopsies. This study aimed to identify non-invasive prognostic biomarkers that differentiat...

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Autores: Sequeiros, Tamara, Bastarós, Juan M., Sánchez, Milagros, Rigau, Marina, Montes, Melania, Placer, José, Planas, Jacques, Torres, Inés de, Reventós Puigjaner, Jaume, Pegtel, D. Michiel, Doll, Andreas, Morote, Juan, Olivan Riera, Mireia
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2015
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/168549
Acceso en línea:https://hdl.handle.net/2445/168549
Access Level:acceso abierto
Palabra clave:Indicadors biològics
Càncer
Orina
Indicators (Biology)
Cancer
Urine
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spelling Urinary biomarkers for the detection of prostate cancer in patients with high-grade prostatic intraepithelial neoplasiaSequeiros, TamaraBastarós, Juan M.Sánchez, MilagrosRigau, MarinaMontes, MelaniaPlacer, JoséPlanas, JacquesTorres, Inés deReventós Puigjaner, JaumePegtel, D. MichielDoll, AndreasMorote, JuanOlivan Riera, MireiaIndicadors biològicsCàncerOrinaIndicators (Biology)CancerUrineIntroduction: high-grade prostatic intraepithelial neoplasia (HGPIN) is a recognized precursor stage of PCa. Men who present HGPIN in a first prostate biopsy face years of active surveillance including repeat biopsies. This study aimed to identify non-invasive prognostic biomarkers that differentiate early on between indolent HGPIN cases and those that will transform into actual PCa. Methods: we measured the expression of 21 candidate mRNA biomarkers using quantitative PCR in urine sediment samples from a cohort of 90 patients with initial diagnosis of HGPIN and a posterior follow up of at least two years. Uni- and multivariate statistical analyses were applied to analyze the candidate biomarkers and multiplex models using combinations of these biomarkers. Results: PSMA, PCA3, PSGR, GOLM, KLK3, CDH1, and SPINK1 behavedas predictors for PCa presence in repeat biopsies. Multiplex models outperformed (AUC = 0.81-0.86) the predictive power of single genes, including the FDA-approved PCA3 (AUC = 0.70). With a fixed sensitivity of 95%, the specificity of our multiplex models was of 41-58%, compared to the 30% of PCA3. The PPV of our models (30-38%) was also higher than the PPV of PCA3 (27%), suggesting that benign cases could be more accurately identified. Applying statistical models, we estimated that 33% to 47% of repeat biopsies could be prevented with a multiplex PCR model, representing an easy applicable and significant advantage over the current gold standard in urine sediment. Discussion: using multiplex RTqPCR-based models in urine sediment it is possible to improve the current diagnostic method of choice (PCA3) to differentiate between benign HGPIN and PCa cases.Wiley2015info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/168549Articles publicats en revistes (Patologia i Terapèutica Experimental)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1002/pros.22995Prostate, 2015, vol. 75, num. 10, p. 1102-1113https://doi.org/10.1002/pros.22995(c) Wiley, 2015info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1685492026-05-27T06:46:51Z
dc.title.none.fl_str_mv Urinary biomarkers for the detection of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia
title Urinary biomarkers for the detection of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia
spellingShingle Urinary biomarkers for the detection of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia
Sequeiros, Tamara
Indicadors biològics
Càncer
Orina
Indicators (Biology)
Cancer
Urine
title_short Urinary biomarkers for the detection of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia
title_full Urinary biomarkers for the detection of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia
title_fullStr Urinary biomarkers for the detection of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia
title_full_unstemmed Urinary biomarkers for the detection of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia
title_sort Urinary biomarkers for the detection of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia
dc.creator.none.fl_str_mv Sequeiros, Tamara
Bastarós, Juan M.
Sánchez, Milagros
Rigau, Marina
Montes, Melania
Placer, José
Planas, Jacques
Torres, Inés de
Reventós Puigjaner, Jaume
Pegtel, D. Michiel
Doll, Andreas
Morote, Juan
Olivan Riera, Mireia
author Sequeiros, Tamara
author_facet Sequeiros, Tamara
Bastarós, Juan M.
Sánchez, Milagros
Rigau, Marina
Montes, Melania
Placer, José
Planas, Jacques
Torres, Inés de
Reventós Puigjaner, Jaume
Pegtel, D. Michiel
Doll, Andreas
Morote, Juan
Olivan Riera, Mireia
author_role author
author2 Bastarós, Juan M.
Sánchez, Milagros
Rigau, Marina
Montes, Melania
Placer, José
Planas, Jacques
Torres, Inés de
Reventós Puigjaner, Jaume
Pegtel, D. Michiel
Doll, Andreas
Morote, Juan
Olivan Riera, Mireia
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Indicadors biològics
Càncer
Orina
Indicators (Biology)
Cancer
Urine
topic Indicadors biològics
Càncer
Orina
Indicators (Biology)
Cancer
Urine
description Introduction: high-grade prostatic intraepithelial neoplasia (HGPIN) is a recognized precursor stage of PCa. Men who present HGPIN in a first prostate biopsy face years of active surveillance including repeat biopsies. This study aimed to identify non-invasive prognostic biomarkers that differentiate early on between indolent HGPIN cases and those that will transform into actual PCa. Methods: we measured the expression of 21 candidate mRNA biomarkers using quantitative PCR in urine sediment samples from a cohort of 90 patients with initial diagnosis of HGPIN and a posterior follow up of at least two years. Uni- and multivariate statistical analyses were applied to analyze the candidate biomarkers and multiplex models using combinations of these biomarkers. Results: PSMA, PCA3, PSGR, GOLM, KLK3, CDH1, and SPINK1 behavedas predictors for PCa presence in repeat biopsies. Multiplex models outperformed (AUC = 0.81-0.86) the predictive power of single genes, including the FDA-approved PCA3 (AUC = 0.70). With a fixed sensitivity of 95%, the specificity of our multiplex models was of 41-58%, compared to the 30% of PCA3. The PPV of our models (30-38%) was also higher than the PPV of PCA3 (27%), suggesting that benign cases could be more accurately identified. Applying statistical models, we estimated that 33% to 47% of repeat biopsies could be prevented with a multiplex PCR model, representing an easy applicable and significant advantage over the current gold standard in urine sediment. Discussion: using multiplex RTqPCR-based models in urine sediment it is possible to improve the current diagnostic method of choice (PCA3) to differentiate between benign HGPIN and PCa cases.
publishDate 2015
dc.date.none.fl_str_mv 2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/168549
url https://hdl.handle.net/2445/168549
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1002/pros.22995
Prostate, 2015, vol. 75, num. 10, p. 1102-1113
https://doi.org/10.1002/pros.22995
dc.rights.none.fl_str_mv (c) Wiley, 2015
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Wiley, 2015
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv Articles publicats en revistes (Patologia i Terapèutica Experimental)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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