RASSF1A and DOK1 Promoter Methylation Levels in Hepatocellular Carcinoma, Cirrhotic and Non-Cirrhotic Liver, and Correlation with Liver Cancer in Brazilian Patients
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2016 |
| Outros Autores: | , , , , , |
| 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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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 |
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2016-06-21T13:27:13Z 2016-07-07T12:11:47Z |
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2016-06-21T13:27:13Z 2016-07-07T12:11:47Z |
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2016 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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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. |
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https://www.arca.fiocruz.br/handle/icict/14667 |
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1932-6203 |
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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 |
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Public Library of Science |
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Public Library of Science |
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