{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T04:31:20Z","timestamp":1790483480963,"version":"4.1.0"},"reference-count":76,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T00:00:00Z","timestamp":1624406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/NEU\/04539\/2019"],"award-info":[{"award-number":["UID\/NEU\/04539\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/ 04539\/2020"],"award-info":[{"award-number":["UIDB\/ 04539\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDP\/04539\/2020"],"award-info":[{"award-number":["UIDP\/04539\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cancers13133138","type":"journal-article","created":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T11:28:41Z","timestamp":1624447721000},"page":"3138","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["DNA Methylation Is Correlated with Oxidative Stress in Myelodysplastic Syndrome\u2014Relevance as Complementary Prognostic Biomarkers"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1470-4802","authenticated-orcid":false,"given":"Ana Cristina","family":"Gon\u00e7alves","sequence":"first","affiliation":[{"name":"Laboratory of Oncobiology and Hematology and University Clinic of Hematology, Faculty of Medicine (FMUC), University of Coimbra, 3000-370 Coimbra, Portugal"},{"name":"Institute for Clinical and Biomedical Research (iCBR)\u2014Group of Environment, Genetics and Oncobiology (CIMAGO), FMUC, University of Coimbra, 3000-370 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-370 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-561 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2599-6433","authenticated-orcid":false,"given":"Raquel","family":"Alves","sequence":"additional","affiliation":[{"name":"Laboratory of Oncobiology and Hematology and University Clinic of Hematology, Faculty of Medicine (FMUC), University of Coimbra, 3000-370 Coimbra, Portugal"},{"name":"Institute for Clinical and Biomedical Research (iCBR)\u2014Group of Environment, Genetics and Oncobiology (CIMAGO), FMUC, University of Coimbra, 3000-370 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-370 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-561 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8106-7308","authenticated-orcid":false,"given":"In\u00eas","family":"Baldeiras","sequence":"additional","affiliation":[{"name":"Faculty of Medicine (FMUC), University of Coimbra, 3000-370 Coimbra, Portugal"},{"name":"Center for Neuroscience and Cell Biology, University of Coimbra, 3000-370 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1rbara","family":"Marques","sequence":"additional","affiliation":[{"name":"Laboratory of Oncobiology and Hematology and University Clinic of Hematology, Faculty of Medicine (FMUC), University of Coimbra, 3000-370 Coimbra, Portugal"},{"name":"Clinical Hematology Department, Centro Hospitalar e Universit\u00e1rio 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Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-370 Coimbra, Portugal"},{"name":"Medicine Department, Hospital da Luz, 3020-479 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Manuel","family":"Nascimento Costa","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Biomedical Research (iCBR)\u2014Group of Environment, Genetics and Oncobiology (CIMAGO), FMUC, University of Coimbra, 3000-370 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-370 Coimbra, Portugal"},{"name":"University Clinic of Oncology, Faculty of Medicine (FMUC), University of Coimbra, 3000-370 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Em\u00edlia","family":"Cortes\u00e3o","sequence":"additional","affiliation":[{"name":"Laboratory of Oncobiology and Hematology and University Clinic of Hematology, Faculty of Medicine (FMUC), University of Coimbra, 3000-370 Coimbra, Portugal"},{"name":"Institute for Clinical and Biomedical Research (iCBR)\u2014Group of Environment, Genetics and Oncobiology (CIMAGO), FMUC, University of Coimbra, 3000-370 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-370 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-561 Coimbra, Portugal"},{"name":"Clinical Hematology Department, Centro Hospitalar e Universit\u00e1rio de Coimbra (CHUC), 3004-561 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Mota Vieira","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Pathology Unit, Hospital do Divino Espirito Santo de Ponta Delgada EPER, S\u00e3o Miguel Island, 9500-370 Azores, Portugal"},{"name":"Faculty of Sciences, BioISI\u2014Biosystems & Integrative Sciences Institute, University of Lisbon, 1649-004 Lisbon, Portugal"},{"name":"Azores Genetics Research Group, Instituto Gulbenkian de Ci\u00eancia, 2780-156 Oeiras, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4142-4841","authenticated-orcid":false,"given":"Ana Bela","family":"Sarmento Ribeiro","sequence":"additional","affiliation":[{"name":"Laboratory of Oncobiology and Hematology and University Clinic of Hematology, Faculty of Medicine (FMUC), University of Coimbra, 3000-370 Coimbra, Portugal"},{"name":"Institute for Clinical and Biomedical Research (iCBR)\u2014Group of Environment, Genetics and Oncobiology (CIMAGO), FMUC, University of Coimbra, 3000-370 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-370 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-561 Coimbra, Portugal"},{"name":"Clinical Hematology Department, Centro Hospitalar e Universit\u00e1rio de Coimbra (CHUC), 3004-561 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