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Related Experiment Video

Updated: May 9, 2025

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
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Plasma Cell-Free DNA Methylation-Based Prognosis in Metastatic Castrate-Resistant Prostate Cancer.

Jodie Wong1, Yijun Tian1, Manishkumar S Patel1

  • 1H. Lee Moffitt Cancer Center.

Research Square
|May 2, 2025
PubMed
Summary

A new prognostic model using cell-free DNA (cfDNA) methylation improves survival prediction for metastatic castration-resistant prostate cancer (mCRPC). This biomarker offers a promising tool for personalized mCRPC treatment strategies.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Prognosticating metastatic castration-resistant prostate cancer (mCRPC) is difficult due to limited validated biomarkers.
  • Accurate molecular prognostication is crucial for tailoring treatment strategies in mCRPC.

Purpose of the Study:

  • To develop and validate a novel prognostic model for mCRPC utilizing plasma cell-free DNA (cfDNA) methylation patterns.
  • To assess the predictive performance of cfDNA methylation biomarkers for overall survival in mCRPC patients.

Main Methods:

  • Targeted cfDNA methylation sequencing was performed on 96 prostate cancer patients across different disease stages.
  • Identified differentially methylated regions, specifically 78 methylation haplotype blocks (MHBs), correlating with cancer progression.
  • Developed a prognostic nomogram integrating MHB-based risk scores, clinical variables, and circulating tumor DNA (ctDNA) fraction.

Main Results:

  • Identified 78 differentially methylated haplotype blocks (MHBs) associated with mCRPC progression.
  • The top 20 MHBs demonstrated significant association with overall survival in mCRPC patients.
  • The developed prognostic nomogram achieved high predictive accuracy for mCRPC survival (AUCs: 0.99 at 6 months, 0.90 at 1 year, 0.87 at 2 years).

Conclusions:

  • Plasma cfDNA methylation serves as a potent molecular biomarker for mCRPC prognostication.
  • The developed cfDNA methylation-based model significantly enhances survival prediction accuracy in mCRPC.
  • This approach holds potential for guiding personalized treatment decisions in advanced prostate cancer.