Cell-Free DNA Modification Dynamics in Abiraterone Acetate-Treated Prostate Cancer Patients

Juozas Gordevičius1, Algimantas Kriščiūnas1, Daniel E Groot2

  • 1Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania.

Insights

New biomarkers in cell-free DNA predict response to abiraterone acetate (AA) treatment in metastatic castration-resistant prostate cancer. Monitoring DNA modification variance offers insights into treatment resistance mechanisms.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Metastatic castration-resistant prostate cancer (mCRPC) treatment relies on abiraterone acetate (AA).
  • Primary resistance to AA occurs in 20-40% of patients, necessitating predictive biomarkers.
  • Understanding resistance mechanisms is crucial for improving patient outcomes.

Purpose of the Study:

  • Identify predictive biomarkers for abiraterone acetate (AA) treatment response in mCRPC.
  • Investigate the mechanisms underlying AA treatment resistance.
  • Explore the prognostic value of cell-free DNA (cfDNA) modification patterns.

Main Methods:

  • Analyzed cfDNA methylation profiles using the Infinium Human Methylation 450K BeadChip.
  • Collected and processed 108 plasma samples from 33 patients with mCRPC treated with AA.
  • Compared cfDNA modification patterns between AA-sensitive and AA-resistant patient groups.

Main Results:

  • Identified 30 cytosines with significant differential modification between AA-sensitive and AA-resistant patients (FDR Q < 0.05).
  • Found that 21 of these cytosines were differentially modified even before treatment initiation.
  • Observed a loss and subsequent return of cfDNA modification interindividual variation in AA-sensitive patients during treatment, unlike in resistant patients.

Conclusions:

  • Discovered potential cfDNA methylation biomarkers for predicting AA treatment response in prostate cancer.
  • Highlighted the prognostic significance of cytosine modification variance in cfDNA.
  • Gained insights into prostate cancer relapse mechanisms in patients initially sensitive to AA.

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