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

Author

Listed:
  • J. K. Wiencke

    (University of California San Francisco)

  • Annette M. Molinaro

    (University of California San Francisco)

  • Gayathri Warrier

    (University of California San Francisco)

  • Terri Rice

    (University of California San Francisco)

  • Jennifer Clarke

    (University of California San Francisco
    University of California San Francisco)

  • Jennie W. Taylor

    (University of California San Francisco
    University of California San Francisco)

  • Margaret Wrensch

    (University of California San Francisco)

  • Helen Hansen

    (University of California San Francisco)

  • Lucie McCoy

    (University of California San Francisco)

  • Emily Tang

    (University of California San Francisco)

  • Stan J. Tamaki

    (University of California San Francisco)

  • Courtney M. Tamaki

    (University of California San Francisco)

  • Emily Nissen

    (University of Kansas Medical Center)

  • Paige Bracci

    (University of California San Francisco)

  • Lucas A. Salas

    (Dartmouth College)

  • Devin C. Koestler

    (University of Kansas Medical Center)

  • Brock C. Christensen

    (Dartmouth College
    Dartmouth College
    Dartmouth College)

  • Ze Zhang

    (Dartmouth College)

  • Karl T. Kelsey

    (Brown University
    Brown University)

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.

Suggested Citation

  • J. K. Wiencke & Annette M. Molinaro & Gayathri Warrier & Terri Rice & Jennifer Clarke & Jennie W. Taylor & Margaret Wrensch & Helen Hansen & Lucie McCoy & Emily Tang & Stan J. Tamaki & Courtney M. Tam, 2022. "DNA methylation as a pharmacodynamic marker of glucocorticoid response and glioma survival," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33215-x
    DOI: 10.1038/s41467-022-33215-x
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    References listed on IDEAS

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