A Model of Epigenetic Biomarkers Based on cfDNA 5mC/5hmC for Early Detection of Colorectal Cancer
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 500
- 试验地点
- 2
- 主要终点
- Sensitivity for detecting colorectal cancer
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Sensitivity for detecting colorectal cancer
时间窗: Baseline (pre-treatment blood sample collection)
Proportion of true positive CRC cases correctly identified by the cfDNA methylation panel.
次要结局
- 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))