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...
| Authors: | ; ; ; ; ; ; ; ; ; ; |
|---|---|
| Format: | Article |
| Status: | Published version |
| Publication date: | 2017 |
| Country: | España |
| Institution: | Universidad de Barcelona |
| Repository: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/120615 |
| Online Access: | https://hdl.handle.net/2445/120615 |
| Access Level: | Open access |
| Keyword: | Marcadors tumorals Micro RNAs Metilació Pronòstic mèdic Càncer de pròstata Tumor markers MicroRNAs Methylation Prognosis Prostate cancer |
| _version_ | 1878733122208530432 |
|---|---|
| author | Torres-Ferreira, Jorge |
| 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 |
| author_browse | Antunes, Luis Bento, Maria José Esteller, Manel, 1968- Freitas, Rui Gómez, Antonio Henrique, Rui Jerónimo, Carmen Menezes, Francisco Duarte Oliveira, Jorge Ramalho-Carvalho, João 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 |
| collection | Dipòsit Digital de la UB |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_507df83e4e89c12e5cea37e04c3f5da7 |
| institution | Universidad de Barcelona |
| instname_str | Universidad de Barcelona |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:diposit.ub.edu:2445/120615 |
| publishDate | 2017 |
| publishDateSort | 2017 |
| publisher | BioMed Central |
| publisherStr | BioMed Central |
| reponame_str | Dipòsit Digital de la UB |
| 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 tumors 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 Marcadors tumorals Micro RNAs Metilació Pronòstic mèdic Càncer de pròstata Tumor markers MicroRNAs Methylation Prognosis Prostate cancer 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. BioMed Central https://hdl.handle.net/2445/120615 |
| 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 |
| status_str | publishedVersion |
| 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 |
| 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_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_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 |
| topic | Marcadors tumorals Micro RNAs Metilació Pronòstic mèdic Càncer de pròstata Tumor markers MicroRNAs Methylation Prognosis Prostate cancer |
| topic_facet | Marcadors tumorals Micro RNAs Metilació Pronòstic mèdic Càncer de pròstata Tumor markers MicroRNAs Methylation Prognosis Prostate cancer |
| url | https://hdl.handle.net/2445/120615 |