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

Nat Commun. 2022 Sep 20;13(1):5505. doi: 10.1038/s41467-022-33215-x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Biomarkers
  • DNA Methylation*
  • Dexamethasone / pharmacology
  • Dexamethasone / therapeutic use
  • Glioma* / drug therapy
  • Glioma* / genetics
  • Glucocorticoids / pharmacology
  • Glucocorticoids / therapeutic use
  • Humans
  • Maleimides
  • Prednisone

Substances

  • Biomarkers
  • Glucocorticoids
  • Maleimides
  • naphthalene-1,5-dimaleimide
  • Dexamethasone
  • Prednisone