| Author | Araújo, Oscar C. | |
| Author | Rosa, Agatha S. | |
| Author | Fernandes, Arlete | |
| Author | Niel, Christian | |
| Author | Nogueira, Cristiane A. Villela | |
| Author | Pannain, Vera | |
| Author | Araujo, Natalia M. | |
| Access date | 2016-06-21T13:27:13Z | pt_BR |
| Access date | 2016-07-07T12:11:47Z | |
| Available date | 2016-06-21T13:27:13Z | pt_BR |
| Available date | 2016-07-07T12:11:47Z | |
| Document date | 2016 | |
| Citation | 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. | pt_BR |
| ISSN | 1932-6203 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/14667 | |
| Language | eng | pt_BR |
| Publisher | Public Library of Science | pt_BR |
| Rights | open access | |
| Title | RASSF1A and DOK1 Promoter Methylation Levels in Hepatocellular Carcinoma, Cirrhotic and Non-Cirrhotic Liver, and Correlation with Liver Cancer in Brazilian Patients | pt_BR |
| Type | Article | |
| DOI | 10.1371/journal.pone.0153796 | pt_BR |
| Abstract | 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. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Hospital Universitário Clementino Fraga Filho. Departamento de Patologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Hospital Universitário Clementino Fraga Filho. Divisão de Hepatologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Hospital Universitário Clementino Fraga Filho. Departamento de Patologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Hepatocellular carcinoma | pt_BR |
| Subject | Methylation | pt_BR |
| Subject | Biomarker | pt_BR |
| Subject | Chronic hepatitis B virus | pt_BR |
| Subject | Hepatitis C virus | pt_BR |
| Subject | Cirrhosis | pt_BR |
| Subject | Brazil | pt_BR |
| DeCS | Carcinoma Hepatocelular | pt_BR |
| DeCS | Metilação | pt_BR |
| DeCS | Virus da Hepatite B | pt_BR |
| DeCS | Virus da Hepatite C | pt_BR |
| DeCS | Brasil | pt_BR |
