DNA Methylation Is Correlated with Oxidative Stress in Myelodysplastic Syndrome-Relevance as Complementary Prognostic Biomarkers

Detalhes bibliográficos
Autor(a) principal: Gonçalves, Ana Cristina
Data de Publicação: 2021
Outros Autores: Alves, Raquel, Baldeiras, Inês, Marques, Bárbara, Oliveiros, Bárbara, Pereira, Amélia, Costa, José Manuel Nascimento, Cortesão, Emília, Vieira, Luísa Mota, Ribeiro, Ana Bela Sarmento
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10316/95820
https://doi.org/10.3390/cancers13133138
Resumo: Oxidative stress and abnormal DNA methylation have been implicated in cancer, including myelodysplastic syndromes (MDSs). This fact leads us to investigate whether oxidative stress is correlated with localized and global DNA methylations in the peripheral blood of MDS patients. Sixty-six MDS patients and 26 healthy individuals were analyzed. Several oxidative stress and macromolecule damage parameters were analyzed. Localized (gene promotor) and global DNA methylations (5-mC and 5-hmC levels; LINE-1 methylation) were assessed. MDS patients had lower levels of reduced glutathione and total antioxidant status (TAS) and higher levels of peroxides, nitric oxide, peroxides/TAS, and 8-hydroxy-2-deoxyguanosine compared with controls. These patients had higher 5-mC levels and lower 5-hmC/5-mC ratio and LINE-1 methylation and increased methylation frequency of at least one methylated gene. Peroxide levels and peroxide/TAS ratio were higher in patients with methylated genes than those without methylation and negatively correlated with LINE-1 methylation and positively with 5-mC levels. The 5-hmC/5-mC ratio was significantly associated with progression to acute leukemia and peroxide/TAS ratio with overall survival. This study points to a relationship between oxidative stress and DNA methylation, two common pathogenic mechanisms involved in MDS, and suggests the relevance of 5-hmC/5-mC and peroxide/TAS ratios as complementary prognostic biomarkers.
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spelling DNA Methylation Is Correlated with Oxidative Stress in Myelodysplastic Syndrome-Relevance as Complementary Prognostic BiomarkersDNA methylationAcute myeloid leukemiaBlood biomarkersMyelodysplastic syndromeOxidative stressPrognosisProgressionSurvivalOxidative stress and abnormal DNA methylation have been implicated in cancer, including myelodysplastic syndromes (MDSs). This fact leads us to investigate whether oxidative stress is correlated with localized and global DNA methylations in the peripheral blood of MDS patients. Sixty-six MDS patients and 26 healthy individuals were analyzed. Several oxidative stress and macromolecule damage parameters were analyzed. Localized (gene promotor) and global DNA methylations (5-mC and 5-hmC levels; LINE-1 methylation) were assessed. MDS patients had lower levels of reduced glutathione and total antioxidant status (TAS) and higher levels of peroxides, nitric oxide, peroxides/TAS, and 8-hydroxy-2-deoxyguanosine compared with controls. These patients had higher 5-mC levels and lower 5-hmC/5-mC ratio and LINE-1 methylation and increased methylation frequency of at least one methylated gene. Peroxide levels and peroxide/TAS ratio were higher in patients with methylated genes than those without methylation and negatively correlated with LINE-1 methylation and positively with 5-mC levels. The 5-hmC/5-mC ratio was significantly associated with progression to acute leukemia and peroxide/TAS ratio with overall survival. This study points to a relationship between oxidative stress and DNA methylation, two common pathogenic mechanisms involved in MDS, and suggests the relevance of 5-hmC/5-mC and peroxide/TAS ratios as complementary prognostic biomarkers.The present work was supported by CIMAGO (Center of Investigation on Environment Genetics and Oncobiology), Faculty of Medicine, University of Coimbra, Portugal; by a grant from Santander-Totta Bank/Gabinete de Apoio/Investigação (GAI) of the Faculty of Medicine, University of Coimbra, Portugal; and by the Foundation for Science and Technology (FCT), PortugalMDPI2021-06-23info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/95820http://hdl.handle.net/10316/95820https://doi.org/10.3390/cancers13133138eng2072-6694Gonçalves, Ana CristinaAlves, RaquelBaldeiras, InêsMarques, BárbaraOliveiros, BárbaraPereira, AméliaCosta, José Manuel NascimentoCortesão, EmíliaVieira, Luísa MotaRibeiro, Ana Bela Sarmentoinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-03-30T09:12:46Zoai:estudogeral.uc.pt:10316/95820Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:14:14.532013Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv DNA Methylation Is Correlated with Oxidative Stress in Myelodysplastic Syndrome-Relevance as Complementary Prognostic Biomarkers
title DNA Methylation Is Correlated with Oxidative Stress in Myelodysplastic Syndrome-Relevance as Complementary Prognostic Biomarkers
spellingShingle DNA Methylation Is Correlated with Oxidative Stress in Myelodysplastic Syndrome-Relevance as Complementary Prognostic Biomarkers
Gonçalves, Ana Cristina
DNA methylation
Acute myeloid leukemia
Blood biomarkers
Myelodysplastic syndrome
Oxidative stress
Prognosis
Progression
Survival
title_short DNA Methylation Is Correlated with Oxidative Stress in Myelodysplastic Syndrome-Relevance as Complementary Prognostic Biomarkers
title_full DNA Methylation Is Correlated with Oxidative Stress in Myelodysplastic Syndrome-Relevance as Complementary Prognostic Biomarkers
title_fullStr DNA Methylation Is Correlated with Oxidative Stress in Myelodysplastic Syndrome-Relevance as Complementary Prognostic Biomarkers
title_full_unstemmed DNA Methylation Is Correlated with Oxidative Stress in Myelodysplastic Syndrome-Relevance as Complementary Prognostic Biomarkers
title_sort DNA Methylation Is Correlated with Oxidative Stress in Myelodysplastic Syndrome-Relevance as Complementary Prognostic Biomarkers
author Gonçalves, Ana Cristina
author_facet Gonçalves, Ana Cristina
Alves, Raquel
Baldeiras, Inês
Marques, Bárbara
Oliveiros, Bárbara
Pereira, Amélia
Costa, José Manuel Nascimento
Cortesão, Emília
Vieira, Luísa Mota
Ribeiro, Ana Bela Sarmento
author_role author
author2 Alves, Raquel
Baldeiras, Inês
Marques, Bárbara
Oliveiros, Bárbara
Pereira, Amélia
Costa, José Manuel Nascimento
Cortesão, Emília
Vieira, Luísa Mota
Ribeiro, Ana Bela Sarmento
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Gonçalves, Ana Cristina
Alves, Raquel
Baldeiras, Inês
Marques, Bárbara
Oliveiros, Bárbara
Pereira, Amélia
Costa, José Manuel Nascimento
Cortesão, Emília
Vieira, Luísa Mota
Ribeiro, Ana Bela Sarmento
dc.subject.por.fl_str_mv DNA methylation
Acute myeloid leukemia
Blood biomarkers
Myelodysplastic syndrome
Oxidative stress
Prognosis
Progression
Survival
topic DNA methylation
Acute myeloid leukemia
Blood biomarkers
Myelodysplastic syndrome
Oxidative stress
Prognosis
Progression
Survival
description Oxidative stress and abnormal DNA methylation have been implicated in cancer, including myelodysplastic syndromes (MDSs). This fact leads us to investigate whether oxidative stress is correlated with localized and global DNA methylations in the peripheral blood of MDS patients. Sixty-six MDS patients and 26 healthy individuals were analyzed. Several oxidative stress and macromolecule damage parameters were analyzed. Localized (gene promotor) and global DNA methylations (5-mC and 5-hmC levels; LINE-1 methylation) were assessed. MDS patients had lower levels of reduced glutathione and total antioxidant status (TAS) and higher levels of peroxides, nitric oxide, peroxides/TAS, and 8-hydroxy-2-deoxyguanosine compared with controls. These patients had higher 5-mC levels and lower 5-hmC/5-mC ratio and LINE-1 methylation and increased methylation frequency of at least one methylated gene. Peroxide levels and peroxide/TAS ratio were higher in patients with methylated genes than those without methylation and negatively correlated with LINE-1 methylation and positively with 5-mC levels. The 5-hmC/5-mC ratio was significantly associated with progression to acute leukemia and peroxide/TAS ratio with overall survival. This study points to a relationship between oxidative stress and DNA methylation, two common pathogenic mechanisms involved in MDS, and suggests the relevance of 5-hmC/5-mC and peroxide/TAS ratios as complementary prognostic biomarkers.
publishDate 2021
dc.date.none.fl_str_mv 2021-06-23
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://hdl.handle.net/10316/95820
http://hdl.handle.net/10316/95820
https://doi.org/10.3390/cancers13133138
url http://hdl.handle.net/10316/95820
https://doi.org/10.3390/cancers13133138
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2072-6694
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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