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DNA methylation as a pharmacodynamic marker of glucocorticoid response and glioma survival

Assessing individual responses to glucocorticoid drug therapies that compromise immune status and affect survival outcomes in neuro-oncology is a great challenge. Here we introduce a blood-based neutrophil dexamethasone methylation index (NDMI) that provides a measure of the epigenetic response of s...

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Autores principales: Wiencke, J. K., Molinaro, Annette M., Warrier, Gayathri, Rice, Terri, Clarke, Jennifer, Taylor, Jennie W., Wrensch, Margaret, Hansen, Helen, McCoy, Lucie, Tang, Emily, Tamaki, Stan J., Tamaki, Courtney M., Nissen, Emily, Bracci, Paige, Salas, Lucas A., Koestler, Devin C., Christensen, Brock C., Zhang, Ze, Kelsey, Karl T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9486797/
https://www.ncbi.nlm.nih.gov/pubmed/36127421
http://dx.doi.org/10.1038/s41467-022-33215-x
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author Wiencke, J. K.
Molinaro, Annette M.
Warrier, Gayathri
Rice, Terri
Clarke, Jennifer
Taylor, Jennie W.
Wrensch, Margaret
Hansen, Helen
McCoy, Lucie
Tang, Emily
Tamaki, Stan J.
Tamaki, Courtney M.
Nissen, Emily
Bracci, Paige
Salas, Lucas A.
Koestler, Devin C.
Christensen, Brock C.
Zhang, Ze
Kelsey, Karl T.
author_facet Wiencke, J. K.
Molinaro, Annette M.
Warrier, Gayathri
Rice, Terri
Clarke, Jennifer
Taylor, Jennie W.
Wrensch, Margaret
Hansen, Helen
McCoy, Lucie
Tang, Emily
Tamaki, Stan J.
Tamaki, Courtney M.
Nissen, Emily
Bracci, Paige
Salas, Lucas A.
Koestler, Devin C.
Christensen, Brock C.
Zhang, Ze
Kelsey, Karl T.
author_sort Wiencke, J. K.
collection PubMed
description Assessing individual responses to glucocorticoid drug therapies that compromise immune status and affect survival outcomes in neuro-oncology is a great challenge. Here we introduce a blood-based neutrophil dexamethasone methylation index (NDMI) that provides a measure of the epigenetic response of subjects to dexamethasone. This marker outperforms conventional approaches based on leukocyte composition as a marker of glucocorticoid response. The NDMI is associated with low CD4 T cells and the accumulation of monocytic myeloid-derived suppressor cells and also serves as prognostic factor in glioma survival. In a non-glioma population, the NDMI increases with a history of prednisone use. Therefore, it may also be informative in other conditions where glucocorticoids are employed. We conclude that DNA methylation remodeling within the peripheral immune compartment is a rich source of clinically relevant markers of glucocorticoid response.
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spelling pubmed-94867972022-09-21 DNA methylation as a pharmacodynamic marker of glucocorticoid response and glioma survival Wiencke, J. K. Molinaro, Annette M. Warrier, Gayathri Rice, Terri Clarke, Jennifer Taylor, Jennie W. Wrensch, Margaret Hansen, Helen McCoy, Lucie Tang, Emily Tamaki, Stan J. Tamaki, Courtney M. Nissen, Emily Bracci, Paige Salas, Lucas A. Koestler, Devin C. Christensen, Brock C. Zhang, Ze Kelsey, Karl T. Nat Commun Article Assessing individual responses to glucocorticoid drug therapies that compromise immune status and affect survival outcomes in neuro-oncology is a great challenge. Here we introduce a blood-based neutrophil dexamethasone methylation index (NDMI) that provides a measure of the epigenetic response of subjects to dexamethasone. This marker outperforms conventional approaches based on leukocyte composition as a marker of glucocorticoid response. The NDMI is associated with low CD4 T cells and the accumulation of monocytic myeloid-derived suppressor cells and also serves as prognostic factor in glioma survival. In a non-glioma population, the NDMI increases with a history of prednisone use. Therefore, it may also be informative in other conditions where glucocorticoids are employed. We conclude that DNA methylation remodeling within the peripheral immune compartment is a rich source of clinically relevant markers of glucocorticoid response. Nature Publishing Group UK 2022-09-20 /pmc/articles/PMC9486797/ /pubmed/36127421 http://dx.doi.org/10.1038/s41467-022-33215-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Wiencke, J. K.
Molinaro, Annette M.
Warrier, Gayathri
Rice, Terri
Clarke, Jennifer
Taylor, Jennie W.
Wrensch, Margaret
Hansen, Helen
McCoy, Lucie
Tang, Emily
Tamaki, Stan J.
Tamaki, Courtney M.
Nissen, Emily
Bracci, Paige
Salas, Lucas A.
Koestler, Devin C.
Christensen, Brock C.
Zhang, Ze
Kelsey, Karl T.
DNA methylation as a pharmacodynamic marker of glucocorticoid response and glioma survival
title DNA methylation as a pharmacodynamic marker of glucocorticoid response and glioma survival
title_full DNA methylation as a pharmacodynamic marker of glucocorticoid response and glioma survival
title_fullStr DNA methylation as a pharmacodynamic marker of glucocorticoid response and glioma survival
title_full_unstemmed DNA methylation as a pharmacodynamic marker of glucocorticoid response and glioma survival
title_short DNA methylation as a pharmacodynamic marker of glucocorticoid response and glioma survival
title_sort dna methylation as a pharmacodynamic marker of glucocorticoid response and glioma survival
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9486797/
https://www.ncbi.nlm.nih.gov/pubmed/36127421
http://dx.doi.org/10.1038/s41467-022-33215-x
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