A Model of Epigenetic Biomarkers Based on cfDNA 5mC/5hmC for Early Detection of Colorectal Cancer
Trial Snapshot
- Phase
- Not Applicable
- Status
- Active, not recruiting
- Sponsor
- Enrollment
- 500
- Locations
- 1
- Primary Endpoint
- Sensitivity for detecting colorectal cancer
Study Overview
Brief Summary
The epiCED is a noninvasive blood-based assay designed for early detection of colorectal cancer (CRC) using circulating cell-free DNA (cfDNA) 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) epigenetic markers. This study leverages retrospective, multi-center cohorts of CRC patients and non-cancer controls to discover and validate a robust cfDNA methylation signature. Small-scale sequencing and machine learning-based modeling will be applied to identify a minimal panel of methylation markers that can accurately discriminate CRC from non-cancer individuals, including early-stage disease. The ultimate goal is to develop a clinically practical, noninvasive screening tool that enables population-level early detection and improves patient outcomes.
Detailed Description
The epiCED is a noninvasive, blood-based approach aimed at early detection of colorectal cancer (CRC) using circulating cell-free DNA (cfDNA) 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) epigenetic markers. Early detection of CRC is critical for improving patient outcomes, but current diagnostic tools-including colonoscopy, CT, and MRI-are either invasive, costly, or insufficiently sensitive for early-stage disease, limiting their use for population-wide screening.
This study will utilize retrospective, multi-center cohorts comprising adult participants (≥18 years) with confirmed CRC and non-cancer controls, including healthy volunteers and individuals with benign gastrointestinal conditions. Blood samples will be subjected to cfDNA extraction and small-scale epigenetic sequencing to profile 5mC and 5hmC patterns.
During the discovery phase, differential methylation analysis and machine learning-based feature selection will be applied to identify a minimal set of cfDNA methylation markers that optimally discriminate CRC from non-cancer individuals. In the training and validation phase, the identified signature will be evaluated across independent international multi-center cohorts to ensure reproducibility, robustness, and early-stage detection performance.
The primary objectives are to:
- Develop a cfDNA methylation panel capable of accurately distinguishing CRC patients from non-cancer controls.
- Validate the panel's ability to detect early-stage CRC.
- Secondary objectives include evaluating the association of the methylation signature with clinical parameters, tumor stage, and demographic factors. By integrating high-resolution cfDNA methylation profiling with advanced computational modeling, epiCED aims to provide a scalable, cost-effective, and clinically practical tool for noninvasive early detection of colorectal cancer.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Retrospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Adults aged ≥18 years at the time of sample collection.
- •Patients with confirmed CRC or non-cancer controls.
- •Availability of retrospective blood samples collected according to institutional protocols.
- •Willingness to allow use of de-identified clinical and demographic data.
Exclusion Criteria
- •Concurrent malignancies outside the gastrointestinal tract (unless in complete remission ≥5 years).
- •Samples with insufficient volume or poor cfDNA quality.
- •Recent chemotherapy, radiotherapy, or major surgery within 4 weeks prior to blood collection (if prospective samples).
- •Any condition precluding reliable sample analysis or participation.
Arms & Interventions
CRC
Adult patients with confirmed colorectal cancer from international centers.
Control
Non-cancer individuals, including healthy volunteers or patients with benign gastrointestinal conditions.
Outcomes
Primary Outcomes
Sensitivity for detecting colorectal cancer
Time Frame: Baseline (pre-treatment blood sample collection)
Proportion of true positive CRC cases correctly identified by the cfDNA methylation panel.
Secondary Outcomes
- Specificity for detecting colorectal cancer(Frame: Baseline (pre-treatment blood sample collection))
- Area Under the Receiver Operating Characteristic Curve (AUROC)(Baseline (pre-treatment blood sample collection))