Prognostic Classifier Based on Genome-Wide DNA Methylation Profiling in Well-Differentiated Thyroid Tumors

Detalhes bibliográficos
Autor(a) principal: Bisarro Dos Reis, Mariana
Data de Publicação: 2017
Outros Autores: Barros-Filho, Mateus Camargo, Marchi, Fábio Albuquerque, Beltrami, Caroline Moraes, Kuasne, Hellen, Pinto, Clóvis Antônio Lopes, Ambatipudi, Srikant, Herceg, Zdenko, Kowalski, Luiz Paulo, Rogatto, Silvia Regina
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1210/jc.2017-00881
http://hdl.handle.net/11449/177069
Resumo: Context: Even though the majority of well-differentiated thyroid carcinoma (WDTC) is indolent, a number of cases display an aggressive behavior. Cumulative evidence suggests that the deregulation of DNA methylation has the potential to point out molecular markers associated with worse prognosis. Objective: To identify a prognostic epigenetic signature in thyroid cancer. Design: Genome-wide DNA methylation assays (450k platform, Illumina) were performed in a cohort of 50 nonneoplastic thyroid tissues (NTs), 17 benign thyroid lesions (BTLs), and 74 thyroid carcinomas (60 papillary, 8 follicular, 2 Hürthle cell, 1 poorly differentiated, and 3 anaplastic). A prognostic classifier for WDTC was developed via diagonal linear discriminant analysis. The results were compared with The Cancer Genome Atlas (TCGA) database. Results: A specific epigenetic profile was detected according to each histological subtype. BTLs and follicular carcinomas showed a greater number of methylated CpG in comparison with NTs, whereas hypomethylation was predominant in papillary and undifferentiated carcinomas. A prognostic classifier based on 21 DNA methylation probes was able to predict poor outcome in patients with WDTC (sensitivity 63%, specificity 92% for internal data; sensitivity 64%, specificity 88% for TCGA data). High-risk score based on the classifier was considered an independent factor of poor outcome (Cox regression, P < 0.001). Conclusions: The methylation profile of thyroid lesions exhibited a specific signature according to the histological subtype. A meaningful algorithm composed of 21 probes was capable of predicting the recurrence in WDTC.
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spelling Prognostic Classifier Based on Genome-Wide DNA Methylation Profiling in Well-Differentiated Thyroid TumorsContext: Even though the majority of well-differentiated thyroid carcinoma (WDTC) is indolent, a number of cases display an aggressive behavior. Cumulative evidence suggests that the deregulation of DNA methylation has the potential to point out molecular markers associated with worse prognosis. Objective: To identify a prognostic epigenetic signature in thyroid cancer. Design: Genome-wide DNA methylation assays (450k platform, Illumina) were performed in a cohort of 50 nonneoplastic thyroid tissues (NTs), 17 benign thyroid lesions (BTLs), and 74 thyroid carcinomas (60 papillary, 8 follicular, 2 Hürthle cell, 1 poorly differentiated, and 3 anaplastic). A prognostic classifier for WDTC was developed via diagonal linear discriminant analysis. The results were compared with The Cancer Genome Atlas (TCGA) database. Results: A specific epigenetic profile was detected according to each histological subtype. BTLs and follicular carcinomas showed a greater number of methylated CpG in comparison with NTs, whereas hypomethylation was predominant in papillary and undifferentiated carcinomas. A prognostic classifier based on 21 DNA methylation probes was able to predict poor outcome in patients with WDTC (sensitivity 63%, specificity 92% for internal data; sensitivity 64%, specificity 88% for TCGA data). High-risk score based on the classifier was considered an independent factor of poor outcome (Cox regression, P < 0.001). Conclusions: The methylation profile of thyroid lesions exhibited a specific signature according to the histological subtype. A meaningful algorithm composed of 21 probes was capable of predicting the recurrence in WDTC.International Research Center, CIPE, A.C. Camargo Cancer Center and National Institute of Science and Technology in Oncogenomics, São Paulo 01509-010, SP, BrazilDepartment of Urology, Faculty of Medicine, UNESP, São Paulo State University, Botucatu 18618-970, SP, BrazilDepartment of Pathology, A.C. Camargo Cancer Center, São Paulo 01509-010, SP, BrazilEpigenetics Group; International Agency for Research on Cancer (IARC), Lyon 69372, FranceMRC Integrative Epidemiology Unit, University of Bristol, Bristol BS8 1TH, United KingdomDepartment of Head and Neck Surgery and Otorhinolaryngology, A.C. Camargo Cancer Center, São Paulo 01509-010, SP, BrazilDepartment of Clinical Genetics, Vejle Hospital and Institute of Regional Health Research, University of Southern Denmark, Vejle, 7100, DenmarkUniversidade Estadual Paulista (Unesp)Bisarro Dos Reis, MarianaBarros-Filho, Mateus CamargoMarchi, Fábio AlbuquerqueBeltrami, Caroline MoraesKuasne, HellenPinto, Clóvis Antônio LopesAmbatipudi, SrikantHerceg, ZdenkoKowalski, Luiz PauloRogatto, Silvia Regina2018-12-11T17:23:43Z2018-12-11T17:23:43Z2017-11-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article4089-4099application/pdfhttp://dx.doi.org/10.1210/jc.2017-00881The Journal of clinical endocrinology and metabolism, v. 102, n. 11, p. 4089-4099, 2017.1945-7197http://hdl.handle.net/11449/17706910.1210/jc.2017-008812-s2.0-850379778222-s2.0-85037977822.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengThe Journal of clinical endocrinology and metabolisminfo:eu-repo/semantics/openAccess2024-09-03T14:30:11Zoai:repositorio.unesp.br:11449/177069Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462024-09-03T14:30:11Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Prognostic Classifier Based on Genome-Wide DNA Methylation Profiling in Well-Differentiated Thyroid Tumors
title Prognostic Classifier Based on Genome-Wide DNA Methylation Profiling in Well-Differentiated Thyroid Tumors
spellingShingle Prognostic Classifier Based on Genome-Wide DNA Methylation Profiling in Well-Differentiated Thyroid Tumors
Bisarro Dos Reis, Mariana
title_short Prognostic Classifier Based on Genome-Wide DNA Methylation Profiling in Well-Differentiated Thyroid Tumors
title_full Prognostic Classifier Based on Genome-Wide DNA Methylation Profiling in Well-Differentiated Thyroid Tumors
title_fullStr Prognostic Classifier Based on Genome-Wide DNA Methylation Profiling in Well-Differentiated Thyroid Tumors
title_full_unstemmed Prognostic Classifier Based on Genome-Wide DNA Methylation Profiling in Well-Differentiated Thyroid Tumors
title_sort Prognostic Classifier Based on Genome-Wide DNA Methylation Profiling in Well-Differentiated Thyroid Tumors
author Bisarro Dos Reis, Mariana
author_facet Bisarro Dos Reis, Mariana
Barros-Filho, Mateus Camargo
Marchi, Fábio Albuquerque
Beltrami, Caroline Moraes
Kuasne, Hellen
Pinto, Clóvis Antônio Lopes
Ambatipudi, Srikant
Herceg, Zdenko
Kowalski, Luiz Paulo
Rogatto, Silvia Regina
author_role author
author2 Barros-Filho, Mateus Camargo
Marchi, Fábio Albuquerque
Beltrami, Caroline Moraes
Kuasne, Hellen
Pinto, Clóvis Antônio Lopes
Ambatipudi, Srikant
Herceg, Zdenko
Kowalski, Luiz Paulo
Rogatto, Silvia Regina
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (Unesp)
dc.contributor.author.fl_str_mv Bisarro Dos Reis, Mariana
Barros-Filho, Mateus Camargo
Marchi, Fábio Albuquerque
Beltrami, Caroline Moraes
Kuasne, Hellen
Pinto, Clóvis Antônio Lopes
Ambatipudi, Srikant
Herceg, Zdenko
Kowalski, Luiz Paulo
Rogatto, Silvia Regina
description Context: Even though the majority of well-differentiated thyroid carcinoma (WDTC) is indolent, a number of cases display an aggressive behavior. Cumulative evidence suggests that the deregulation of DNA methylation has the potential to point out molecular markers associated with worse prognosis. Objective: To identify a prognostic epigenetic signature in thyroid cancer. Design: Genome-wide DNA methylation assays (450k platform, Illumina) were performed in a cohort of 50 nonneoplastic thyroid tissues (NTs), 17 benign thyroid lesions (BTLs), and 74 thyroid carcinomas (60 papillary, 8 follicular, 2 Hürthle cell, 1 poorly differentiated, and 3 anaplastic). A prognostic classifier for WDTC was developed via diagonal linear discriminant analysis. The results were compared with The Cancer Genome Atlas (TCGA) database. Results: A specific epigenetic profile was detected according to each histological subtype. BTLs and follicular carcinomas showed a greater number of methylated CpG in comparison with NTs, whereas hypomethylation was predominant in papillary and undifferentiated carcinomas. A prognostic classifier based on 21 DNA methylation probes was able to predict poor outcome in patients with WDTC (sensitivity 63%, specificity 92% for internal data; sensitivity 64%, specificity 88% for TCGA data). High-risk score based on the classifier was considered an independent factor of poor outcome (Cox regression, P < 0.001). Conclusions: The methylation profile of thyroid lesions exhibited a specific signature according to the histological subtype. A meaningful algorithm composed of 21 probes was capable of predicting the recurrence in WDTC.
publishDate 2017
dc.date.none.fl_str_mv 2017-11-01
2018-12-11T17:23:43Z
2018-12-11T17:23:43Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1210/jc.2017-00881
The Journal of clinical endocrinology and metabolism, v. 102, n. 11, p. 4089-4099, 2017.
1945-7197
http://hdl.handle.net/11449/177069
10.1210/jc.2017-00881
2-s2.0-85037977822
2-s2.0-85037977822.pdf
url http://dx.doi.org/10.1210/jc.2017-00881
http://hdl.handle.net/11449/177069
identifier_str_mv The Journal of clinical endocrinology and metabolism, v. 102, n. 11, p. 4089-4099, 2017.
1945-7197
10.1210/jc.2017-00881
2-s2.0-85037977822
2-s2.0-85037977822.pdf
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv The Journal of clinical endocrinology and metabolism
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 4089-4099
application/pdf
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv repositoriounesp@unesp.br
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