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5-Hydroxymethylated Biomarkers in Cell-Free DNA Predict Occult Colorectal Cancer up to 36 Months Before Diagnosis in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

  • 0Department of Chemistry, The University of Chicago, Chicago, IL.
Jco Precision Oncology +

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October 11, 2024

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October 11, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

New epigenetic biomarkers in cell-free DNA (cfDNA) can detect colorectal cancer (CRC) up to 36 months before diagnosis. This minimally invasive approach shows promise for improving early CRC detection and patient outcomes.

Area Of Science

  • Epigenetics
  • Molecular Oncology
  • Biomarker Discovery

Background

  • Early detection of colorectal cancer (CRC) is crucial for improving patient outcomes.
  • Current screening methods have limitations in sensitivity and accessibility.
  • Identifying novel biomarkers for pre-symptomatic CRC detection is a significant unmet need.

Purpose Of The Study

  • To identify cell-free DNA (cfDNA) biomarkers with 5-hydroxymethylcytosine (5hmC) modifications for early detection of colorectal cancer (CRC).
  • To evaluate the predictive performance of these 5hmC biomarkers for detecting CRC up to 36 months prior to clinical diagnosis.

Main Methods

  • Utilized plasma samples from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.
  • Performed 5hmC-seal assay and sequencing on cfDNA from 201 CRC cases and 401 controls.
  • Employed association studies and machine learning modeling on genome-wide 5hmC profiles.

Main Results

  • Successfully obtained 5hmC profiles from historical samples.
  • A weighted Cox model of 32 5hmC-modified gene bodies predicted CRC up to 36 months pre-diagnosis (AUC 77.1% training, 72.8% validation).
  • The 5hmC predictive model outperformed traditional risk factors and showed significant risk stratification.

Conclusions

  • Candidate 5hmC biomarkers and a scoring algorithm show potential for predicting CRC occurrence before clinical symptoms.
  • A minimally invasive assay detecting 5hmC biomarkers could significantly improve early CRC detection.
  • This approach holds promise for enhancing patient outcomes through earlier intervention.