RASSF1A and DOK1 Promoter Methylation Levels in Hepatocellular Carcinoma, Cirrhotic and Non-Cirrhotic Liver, and Correlation with Liver Cancer in Brazilian Patients

Detalhes bibliográficos
Autor(a) principal: Araújo, Oscar C.
Data de Publicação: 2016
Outros Autores: Rosa, Agatha S., Fernandes, Arlete, Niel, Christian, Nogueira, Cristiane A. Villela, Pannain, Vera, Araujo, Natalia M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/14667
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil.
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spelling Araújo, Oscar C.Rosa, Agatha S.Fernandes, ArleteNiel, ChristianNogueira, Cristiane A. VillelaPannain, VeraAraujo, Natalia M.2016-06-21T13:27:13Z2016-07-07T12:11:47Z2016-06-21T13:27:13Z2016-07-07T12:11:47Z2016ARAÚJO, Oscar C. et al. RASSF1A and DOK1 Promoter Methylation Levels in Hepatocellular Carcinoma, Cirrhotic and Non-Cirrhotic Liver, and Correlation with Liver Cancer in Brazilian Patients. Plos One, v.11, n.4, e0153796, 10p, Apr. 2016.1932-6203https://www.arca.fiocruz.br/handle/icict/1466710.1371/journal.pone.0153796engPublic Library of ScienceRASSF1A and DOK1 Promoter Methylation Levels in Hepatocellular Carcinoma, Cirrhotic and Non-Cirrhotic Liver, and Correlation with Liver Cancer in Brazilian Patientsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Hospital Universitário Clementino Fraga Filho. Departamento de Patologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Hospital Universitário Clementino Fraga Filho. Divisão de Hepatologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Hospital Universitário Clementino Fraga Filho. Departamento de Patologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil.Hepatocellular carcinoma (HCC) is the second most common cause of cancer mortality worldwide. Most cases of HCC are associated with cirrhosis related to chronic hepatitis B virus or hepatitis C virus infections. Hypermethylation of promoter regions is the main epigenetic mechanism of gene silencing and has been involved in HCC development. The aim of this study was to determine whether aberrant methylation of RASSF1A and DOK1 gene promoters is associated with the progression of liver disease in Brazilian patients. Methylation levels were measured by pyrosequencing in 41 (20 HCC, 9 cirrhotic, and 12 non-cirrhotic) liver tissue samples. Mean rates of methylation in RASSF1A and DOK1 were 16.2%and 12.0% in non-cirrhotic, 26.1% and 19.6%in cirrhotic, and 59.1%and 56.0% in HCC tissues, respectively, showing a gradual increase according to the progression of the disease, with significantly higher levels in tumor tissues. In addition, hypermethylation of RASSF1A and DOK1 was found in the vast majority (88%) of the HCC cases. Interestingly, DOK1 methylation levels in HCC samples were significantly higher in the group of younger (<40 years) patients, and higher in moderately differentiated than in poorly differentiated tumors (p < 0.05). Our results reinforce the hypothesis that hypermethylation of RASSF1A and DOK1 contributes to hepatocarcinogenesis and is associated to clinicopathological characteristics. RASSF1A and DOK1 promoter hypermethylation may be a valuable biomarker for early diagnosis of HCC and a potential molecular target for epigenetic-based therapy.Hepatocellular carcinomaMethylationBiomarkerChronic hepatitis B virusHepatitis C virusCirrhosisBrazilCarcinoma HepatocelularMetilaçãoVirus da Hepatite BVirus da Hepatite CBrasilinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZTEXToscar_araujo_etla_IOC_2016.PDF.txtoscar_araujo_etla_IOC_2016.PDF.txtExtracted 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dc.title.pt_BR.fl_str_mv RASSF1A and DOK1 Promoter Methylation Levels in Hepatocellular Carcinoma, Cirrhotic and Non-Cirrhotic Liver, and Correlation with Liver Cancer in Brazilian Patients
title RASSF1A and DOK1 Promoter Methylation Levels in Hepatocellular Carcinoma, Cirrhotic and Non-Cirrhotic Liver, and Correlation with Liver Cancer in Brazilian Patients
spellingShingle RASSF1A and DOK1 Promoter Methylation Levels in Hepatocellular Carcinoma, Cirrhotic and Non-Cirrhotic Liver, and Correlation with Liver Cancer in Brazilian Patients
Araújo, Oscar C.
Hepatocellular carcinoma
Methylation
Biomarker
Chronic hepatitis B virus
Hepatitis C virus
Cirrhosis
Brazil
Carcinoma Hepatocelular
Metilação
Virus da Hepatite B
Virus da Hepatite C
Brasil
title_short RASSF1A and DOK1 Promoter Methylation Levels in Hepatocellular Carcinoma, Cirrhotic and Non-Cirrhotic Liver, and Correlation with Liver Cancer in Brazilian Patients
title_full RASSF1A and DOK1 Promoter Methylation Levels in Hepatocellular Carcinoma, Cirrhotic and Non-Cirrhotic Liver, and Correlation with Liver Cancer in Brazilian Patients
title_fullStr RASSF1A and DOK1 Promoter Methylation Levels in Hepatocellular Carcinoma, Cirrhotic and Non-Cirrhotic Liver, and Correlation with Liver Cancer in Brazilian Patients
title_full_unstemmed RASSF1A and DOK1 Promoter Methylation Levels in Hepatocellular Carcinoma, Cirrhotic and Non-Cirrhotic Liver, and Correlation with Liver Cancer in Brazilian Patients
title_sort RASSF1A and DOK1 Promoter Methylation Levels in Hepatocellular Carcinoma, Cirrhotic and Non-Cirrhotic Liver, and Correlation with Liver Cancer in Brazilian Patients
author Araújo, Oscar C.
author_facet Araújo, Oscar C.
Rosa, Agatha S.
Fernandes, Arlete
Niel, Christian
Nogueira, Cristiane A. Villela
Pannain, Vera
Araujo, Natalia M.
author_role author
author2 Rosa, Agatha S.
Fernandes, Arlete
Niel, Christian
Nogueira, Cristiane A. Villela
Pannain, Vera
Araujo, Natalia M.
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Araújo, Oscar C.
Rosa, Agatha S.
Fernandes, Arlete
Niel, Christian
Nogueira, Cristiane A. Villela
Pannain, Vera
Araujo, Natalia M.
dc.subject.en.pt_BR.fl_str_mv Hepatocellular carcinoma
Methylation
Biomarker
Chronic hepatitis B virus
Hepatitis C virus
Cirrhosis
Brazil
topic Hepatocellular carcinoma
Methylation
Biomarker
Chronic hepatitis B virus
Hepatitis C virus
Cirrhosis
Brazil
Carcinoma Hepatocelular
Metilação
Virus da Hepatite B
Virus da Hepatite C
Brasil
dc.subject.decs.pt_BR.fl_str_mv Carcinoma Hepatocelular
Metilação
Virus da Hepatite B
Virus da Hepatite C
Brasil
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil.
publishDate 2016
dc.date.accessioned.fl_str_mv 2016-06-21T13:27:13Z
2016-07-07T12:11:47Z
dc.date.available.fl_str_mv 2016-06-21T13:27:13Z
2016-07-07T12:11:47Z
dc.date.issued.fl_str_mv 2016
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.citation.fl_str_mv ARAÚJO, Oscar C. et al. RASSF1A and DOK1 Promoter Methylation Levels in Hepatocellular Carcinoma, Cirrhotic and Non-Cirrhotic Liver, and Correlation with Liver Cancer in Brazilian Patients. Plos One, v.11, n.4, e0153796, 10p, Apr. 2016.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/14667
dc.identifier.issn.pt_BR.fl_str_mv 1932-6203
dc.identifier.doi.pt_BR.fl_str_mv 10.1371/journal.pone.0153796
identifier_str_mv ARAÚJO, Oscar C. et al. RASSF1A and DOK1 Promoter Methylation Levels in Hepatocellular Carcinoma, Cirrhotic and Non-Cirrhotic Liver, and Correlation with Liver Cancer in Brazilian Patients. Plos One, v.11, n.4, e0153796, 10p, Apr. 2016.
1932-6203
10.1371/journal.pone.0153796
url https://www.arca.fiocruz.br/handle/icict/14667
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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