Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/108733
DC Field | Value | Language |
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dc.contributor.author | Castelo Branco, Pedro | - |
dc.contributor.author | Leão, Ricardo | - |
dc.contributor.author | Lipman, Tatiana | - |
dc.contributor.author | Campbell, Brittany | - |
dc.contributor.author | Lee, Donghyun | - |
dc.contributor.author | Price, Aryeh | - |
dc.contributor.author | Zhang, Cindy | - |
dc.contributor.author | Heidari, Abolfazl | - |
dc.contributor.author | Stephens, Derek | - |
dc.contributor.author | Boerno, Stefan | - |
dc.contributor.author | Coelho, Hugo | - |
dc.contributor.author | Gomes, Ana | - |
dc.contributor.author | Domingos, Celia | - |
dc.contributor.author | Apolonio, Joana D | - |
dc.contributor.author | Schäfer, Georg | - |
dc.contributor.author | Bristow, Robert G | - |
dc.contributor.author | Schweiger, Michal R | - |
dc.contributor.author | Hamilton, Robert | - |
dc.contributor.author | Zlotta, Alexandre | - |
dc.contributor.author | Figueiredo, Arnaldo | - |
dc.contributor.author | Klocker, Helmut | - |
dc.contributor.author | Sültmann, Holger | - |
dc.contributor.author | Tabori, Uri | - |
dc.date.accessioned | 2023-09-11T10:31:43Z | - |
dc.date.available | 2023-09-11T10:31:43Z | - |
dc.date.issued | 2016-09-06 | - |
dc.identifier.issn | 1949-2553 | pt |
dc.identifier.uri | https://hdl.handle.net/10316/108733 | - |
dc.description.abstract | The identification of new biomarkers to differentiate between indolent and aggressive prostate tumors is an important unmet need. We examined the role of THOR (TERT Hypermethylated Oncological Region) as a diagnostic and prognostic biomarker in prostate cancer (PCa).We analyzed THOR in common cancers using genome-wide methylation arrays. Methylation status of the whole TERT gene in benign and malignant prostate samples was determined by MeDIP-Seq. The prognostic role of THOR in PCa was assessed by pyrosequencing on discovery and validation cohorts from patients who underwent radical prostatectomy with long-term follow-up data.Most cancers (n = 3056) including PCa (n = 300) exhibited hypermethylation of THOR. THOR was the only region within the TERT gene that is differentially methylated between normal and malignant prostate tissue (p < 0.0001). Also, THOR was significantly hypermethylated in PCa when compared to paired benign tissues (n = 164, p < 0.0001). THOR hypermethylation correlated with Gleason scores and was associated with tumor invasiveness (p = 0.0147). Five years biochemical progression free survival (BPFS) for PCa patients in the discovery cohort was 87% (95% CI 73-100) and 65% (95% CI 52-78) for THOR non-hypermethylated and hypermethylated cancers respectively (p = 0.01). Similar differences in BPFS were noted in the validation cohort (p = 0.03). Importantly, THOR was able to predict outcome in the challenging (Gleason 6 and 7 (3 + 4)) PCa (p = 0.007). For this group, THOR was an independent risk factor for BPFS with a hazard-ratio of 3.685 (p = 0.0247). Finally, THOR hypermethylation more than doubled the risk of recurrence across all PSA levels (OR 2.5, p = 0.02). | pt |
dc.language.iso | eng | pt |
dc.publisher | Impact Journals | pt |
dc.relation | The Canadian Institute of Health Research; | pt |
dc.relation | Canadian Cancer Society Research Institute, | pt |
dc.relation | MaRS Innovation | pt |
dc.relation | UID/BIM/04773/2013 CBMR 1334 | pt |
dc.relation | SFRH/BD/102232/2014 | pt |
dc.relation | Volkswagenstiftung (Lichtenberg Program) | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt |
dc.subject | TERT | pt |
dc.subject | prostate cancer | pt |
dc.subject | biomarker | pt |
dc.subject | diagnostic | pt |
dc.subject | Gleason score | pt |
dc.subject.mesh | Aged | pt |
dc.subject.mesh | Biomarkers, Tumor | pt |
dc.subject.mesh | Cell Differentiation | pt |
dc.subject.mesh | DNA Methylation | pt |
dc.subject.mesh | Epigenesis, Genetic | pt |
dc.subject.mesh | Follow-Up Studies | pt |
dc.subject.mesh | Gene Expression Regulation, Neoplastic | pt |
dc.subject.mesh | Humans | pt |
dc.subject.mesh | Male | pt |
dc.subject.mesh | Middle Aged | pt |
dc.subject.mesh | Neoplasm Recurrence, Local | pt |
dc.subject.mesh | Prognosis | pt |
dc.subject.mesh | Proportional Hazards Models | pt |
dc.subject.mesh | Prostatectomy | pt |
dc.subject.mesh | Prostatic Neoplasms | pt |
dc.subject.mesh | Retrospective Studies | pt |
dc.subject.mesh | Telomerase | pt |
dc.title | A cancer specific hypermethylation signature of the TERT promoter predicts biochemical relapse in prostate cancer: a retrospective cohort study | pt |
dc.type | article | - |
degois.publication.firstPage | 57726 | pt |
degois.publication.lastPage | 57736 | pt |
degois.publication.issue | 36 | pt |
degois.publication.title | Oncotarget | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.18632/oncotarget.10639 | pt |
degois.publication.volume | 7 | pt |
dc.date.embargo | 2016-09-06 | * |
uc.date.periodoEmbargo | 0 | pt |
item.fulltext | Com Texto completo | - |
item.languageiso639-1 | en | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.openairetype | article | - |
item.grantfulltext | open | - |
item.cerifentitytype | Publications | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.orcid | 0000-0002-3453-3978 | - |
crisitem.author.orcid | 0000-0003-3719-717X | - |
crisitem.author.orcid | 0000-0002-7157-0081 | - |
crisitem.author.orcid | 0000-0002-5019-2683 | - |
Appears in Collections: | FMUC Medicina - Artigos em Revistas Internacionais |
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A-cancer-specific-hypermethylation-signature-of-the-TERT-promoter-predicts-biochemical-relapse-in-prostate-cancer-A-retrospective-cohort-studyOncotarget.pdf | 7.13 MB | Adobe PDF | View/Open |
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