MiR-193b promoter methylation accurately detects prostate cancer in urine sediments and miR-34b/c or miR-129-2 promoter methylation define subsets of clinically aggressive tumors

Background: contemporary challenges of prostate cancer (PCa) include overdiagnosis and overtreatment, entailing the need for novel clinical tools to improve risk stratification and therapy selection. PCa diagnosis and prognostication might be perfected using epigenetic biomarkers, among which aberra...

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Autores: Torres-Ferreira, Jorge, Ramalho-Carvalho, João, Gómez, Antonio, Menezes, Francisco Duarte, Freitas, Rui, Oliveira, Jorge, Antunes, Luis, Bento, Maria José, Esteller, Manel, 1968-, Henrique, Rui, Jerónimo, Carmen
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/120615
Acceso en línea:https://hdl.handle.net/2445/120615
Access Level:acceso abierto
Palabra clave:Marcadors tumorals
Micro RNAs
Metilació
Pronòstic mèdic
Càncer de pròstata
Tumor markers
MicroRNAs
Methylation
Prognosis
Prostate cancer
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spelling MiR-193b promoter methylation accurately detects prostate cancer in urine sediments and miR-34b/c or miR-129-2 promoter methylation define subsets of clinically aggressive tumorsTorres-Ferreira, JorgeRamalho-Carvalho, JoãoGómez, AntonioMenezes, Francisco DuarteFreitas, RuiOliveira, JorgeAntunes, LuisBento, Maria JoséEsteller, Manel, 1968-Henrique, RuiJerónimo, CarmenMarcadors tumoralsMicro RNAsMetilacióPronòstic mèdicCàncer de pròstataTumor markersMicroRNAsMethylationPrognosisProstate cancerBackground: contemporary challenges of prostate cancer (PCa) include overdiagnosis and overtreatment, entailing the need for novel clinical tools to improve risk stratification and therapy selection. PCa diagnosis and prognostication might be perfected using epigenetic biomarkers, among which aberrant DNA methylation of microRNA promoters has not been systematically explored. Herein, we identified aberrantly methylated microRNAs promoters in PCa and assessed its diagnostic and prognostic biomarker potential. Methods: using HumanMethylation450 BeadChip-based analysis differentially methylated CpGs in microRNA promoters were identified. Promoter methylation of six microRNAs (miR-34b/c, miR-129-2, miR-152, miR-193b, miR-663a and miR-1258) was analyzed by qMSP in three sets (180 prostatectomies, 95 urine sediments and 74 prostate biopsies). Biomarkers' diagnostic (validity estimates) and prognostic [disease-free (DFS) and disease-specific survival (DSS)] performance was assessed. Results: significantly higher promoter methylation levels in PCa were confirmed for six candidate microRNAs. Except for miR-152, all displayed AUC values higher than 0.90, with miR-1258 and miR-193b disclosing the best performance (AUC = 0.99 and AUC = 0.96, respectively). In urine samples, miR-193b showed the best performance (91.6% sensitivity, 95.7% specificity, AUC = 0.96). Moreover, higher miR-129-2 independently predicted for shorter DSS and miR−34b/c methylation levels independently predicted for shorter DFS and DSS. Conclusions: quantitative miR-193b, miR-129-2 and miR-34b/c promoter methylation might be clinically useful PCa biomarkers for non-invasive detection/diagnosis and prognostication, both in tissue and urine samples.BioMed Central2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/120615Articles publicats en revistes (Ciències Fisiològiques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1186/s12943-017-0604-0Molecular Cancer, 2017, vol. 16, num. 1, p. 26https://doi.org/10.1186/s12943-017-0604-0cc-by (c) Torres-Ferreira, Jorge et al., 2017http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1206152026-05-27T06:46:51Z
dc.title.none.fl_str_mv MiR-193b promoter methylation accurately detects prostate cancer in urine sediments and miR-34b/c or miR-129-2 promoter methylation define subsets of clinically aggressive tumors
title MiR-193b promoter methylation accurately detects prostate cancer in urine sediments and miR-34b/c or miR-129-2 promoter methylation define subsets of clinically aggressive tumors
spellingShingle MiR-193b promoter methylation accurately detects prostate cancer in urine sediments and miR-34b/c or miR-129-2 promoter methylation define subsets of clinically aggressive tumors
Torres-Ferreira, Jorge
Marcadors tumorals
Micro RNAs
Metilació
Pronòstic mèdic
Càncer de pròstata
Tumor markers
MicroRNAs
Methylation
Prognosis
Prostate cancer
title_short MiR-193b promoter methylation accurately detects prostate cancer in urine sediments and miR-34b/c or miR-129-2 promoter methylation define subsets of clinically aggressive tumors
title_full MiR-193b promoter methylation accurately detects prostate cancer in urine sediments and miR-34b/c or miR-129-2 promoter methylation define subsets of clinically aggressive tumors
title_fullStr MiR-193b promoter methylation accurately detects prostate cancer in urine sediments and miR-34b/c or miR-129-2 promoter methylation define subsets of clinically aggressive tumors
title_full_unstemmed MiR-193b promoter methylation accurately detects prostate cancer in urine sediments and miR-34b/c or miR-129-2 promoter methylation define subsets of clinically aggressive tumors
title_sort MiR-193b promoter methylation accurately detects prostate cancer in urine sediments and miR-34b/c or miR-129-2 promoter methylation define subsets of clinically aggressive tumors
dc.creator.none.fl_str_mv Torres-Ferreira, Jorge
Ramalho-Carvalho, João
Gómez, Antonio
Menezes, Francisco Duarte
Freitas, Rui
Oliveira, Jorge
Antunes, Luis
Bento, Maria José
Esteller, Manel, 1968-
Henrique, Rui
Jerónimo, Carmen
author Torres-Ferreira, Jorge
author_facet Torres-Ferreira, Jorge
Ramalho-Carvalho, João
Gómez, Antonio
Menezes, Francisco Duarte
Freitas, Rui
Oliveira, Jorge
Antunes, Luis
Bento, Maria José
Esteller, Manel, 1968-
Henrique, Rui
Jerónimo, Carmen
author_role author
author2 Ramalho-Carvalho, João
Gómez, Antonio
Menezes, Francisco Duarte
Freitas, Rui
Oliveira, Jorge
Antunes, Luis
Bento, Maria José
Esteller, Manel, 1968-
Henrique, Rui
Jerónimo, Carmen
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Marcadors tumorals
Micro RNAs
Metilació
Pronòstic mèdic
Càncer de pròstata
Tumor markers
MicroRNAs
Methylation
Prognosis
Prostate cancer
topic Marcadors tumorals
Micro RNAs
Metilació
Pronòstic mèdic
Càncer de pròstata
Tumor markers
MicroRNAs
Methylation
Prognosis
Prostate cancer
description Background: contemporary challenges of prostate cancer (PCa) include overdiagnosis and overtreatment, entailing the need for novel clinical tools to improve risk stratification and therapy selection. PCa diagnosis and prognostication might be perfected using epigenetic biomarkers, among which aberrant DNA methylation of microRNA promoters has not been systematically explored. Herein, we identified aberrantly methylated microRNAs promoters in PCa and assessed its diagnostic and prognostic biomarker potential. Methods: using HumanMethylation450 BeadChip-based analysis differentially methylated CpGs in microRNA promoters were identified. Promoter methylation of six microRNAs (miR-34b/c, miR-129-2, miR-152, miR-193b, miR-663a and miR-1258) was analyzed by qMSP in three sets (180 prostatectomies, 95 urine sediments and 74 prostate biopsies). Biomarkers' diagnostic (validity estimates) and prognostic [disease-free (DFS) and disease-specific survival (DSS)] performance was assessed. Results: significantly higher promoter methylation levels in PCa were confirmed for six candidate microRNAs. Except for miR-152, all displayed AUC values higher than 0.90, with miR-1258 and miR-193b disclosing the best performance (AUC = 0.99 and AUC = 0.96, respectively). In urine samples, miR-193b showed the best performance (91.6% sensitivity, 95.7% specificity, AUC = 0.96). Moreover, higher miR-129-2 independently predicted for shorter DSS and miR−34b/c methylation levels independently predicted for shorter DFS and DSS. Conclusions: quantitative miR-193b, miR-129-2 and miR-34b/c promoter methylation might be clinically useful PCa biomarkers for non-invasive detection/diagnosis and prognostication, both in tissue and urine samples.
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/120615
url https://hdl.handle.net/2445/120615
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1186/s12943-017-0604-0
Molecular Cancer, 2017, vol. 16, num. 1, p. 26
https://doi.org/10.1186/s12943-017-0604-0
dc.rights.none.fl_str_mv cc-by (c) Torres-Ferreira, Jorge et al., 2017
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Torres-Ferreira, Jorge et al., 2017
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
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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