Application of Polygenic Methylation Markers in Postoperative Recurrence Monitoring of Colorectal Cancer

Based on the Application of Peripheral Blood Polygene Methylation Markers in Postoperative Recurrence Monitoring of Colorectal Cancer

This study dynamically monitored the prognosis of stage I-IV colorectal cancer patients who could receive radical surgical resection by detecting the levels of polygene methylation in plasma samples from patients with colorectal cancer. In patients with colorectal cancer feasible radical surgery, plasma ctDNA methylation detection was performed before and after surgical treatment and during regular follow-up to explore the predictive effect of plasma ctDNA methylation status at different time points on postoperative recurrence. To explore whether postoperative dynamic monitoring of plasma ctDNA methylation can be used for adjuvant chemotherapy efficacy evaluation and whether it can indicate tumor recurrence and metastasis earlier than imaging examination.

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Cancer

Detailed Description

1. Patients initially diagnosed with primary colorectal cancer were enrolled for screening, and plasma samples 1-2 days before radical bowel resection were collected for polygene methylation detection.
2. The postoperative follow-up was 2 years, and the reexamination included CT/MRI imaging assessment, blood CEA, and dynamic monitoring of plasma ctDNA methylation level. Blood samples were collected for 9 times.
3. Results analysis: To explore the application value of ctDNA methylation-MRD detection in the prediction of postoperative tumor recurrence risk after radical resection of colorectal cancer; The correlation between preoperative ctDNA methylation level and prognosis of early colorectal cancer.

• Study Type: Observational
• Enrollment (Estimated): 800

Contacts and Locations

Study Locations

• China
  • Chengdu, China
    • West China hospital
  • Guangzhou, China
    • Sun Yat-sen University Cancer Center
  • Haerbin, China
    • The Second Affiliated Hospital of Harbin Medical University
  • Shanghai, China
    • The First Affiliated Hospital of Naval Medical University/ Changhai Hospital
  • Shenzhen, China
    • Chinese Academy of Medical Sciences, Shenzhen Center
  • Taiyuan, China
    • Shanxi Cancer hospital (Shanxi Cancer institute)
  • Beijing
    • Beijing, Beijing, China, 100029
      • Cancer Hospital Chinese Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

800 patients with initial clinical diagnosis of primary colorectal cancer

Description

Inclusion Criteria:

1. Newly diagnosed patients with primary colorectal cancer confirmed by histopathology (no restriction on histological type);
2. Patients diagnosed as stage I-III and feasible for radical bowel surgery;
3. Patients diagnosed by stage IV (only colorectal cancer patients with liver metastasis at the time of diagnosis) and feasible radical bowel resection or complete resection of liver metastasis;
4. No gender limitation, age ≥18;
5. ECOG score ≤1;
6. Life expectancy ≥5 years;
7. Those who fully understand the study and voluntarily sign the informed consent.

Exclusion Criteria:

1. Blood transfusion was performed during surgery or 2 weeks before surgery;
2. complicated with primary malignant tumors of other organs;
3. With colonic obstruction, intestinal perforation and other symptoms requiring emergency treatment;
4. Colorectal cancer was diagnosed with extrahepatic metastasis;
5. Neoadjuvant therapy (such as radiotherapy and chemotherapy) before radical bowel resection;
6. Radical bowel resection was performed after endoscopic surgery;
7. Concomitant symptoms and/or family history collection suggest hereditary colorectal cancer;
8. serious mental illness or drug abuse;
9. patients with serious heart, lung and vascular diseases who cannot tolerate surgery;
10. pregnant or lactating women;
11. Participate in other interventional clinical investigators within 3 months
12. Poor compliance, unable to complete the study according to the judgment of the researcher.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
MRD positive group; ColonAiQ polygene methylation test was performed on peripheral blood plasma samples from the enrolled patients 4 weeks after surgery. If gene methylation levels in the samples exceeded the threshold, the patients were enrolled in the MRD positive group. The 2-year total tumor recurrence rate of patients in the MRD positive group was calculated, and the positive prediction rate of postoperative plasma ctDNA methylation-MRD detection results for 2-year tumor recurrence rate after colorectal cancer radical resection was calculated.
MRD negative group; ColonAiQ polygene methylation test was performed on peripheral blood plasma samples from the enrolled patients 4 weeks after surgery. If the gene methylation level detected in the samples did not exceed the threshold, the patients were enrolled in the MRD negative group. The 2-year total tumor recurrence rate of patients in the negative MRD group was calculated, and the negative prediction rate of postoperative plasma ctDNA methylation-MRD test results for 2-year tumor recurrence rate after radical resection of colorectal cancer was calculated.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To investigate the prediction and monitoring effect of plasma ctDNA methylation on postoperative recurrence of primary colorectal cancer patients after radical surgery	To investigate the role of peripheral plasma ctDNA methylation level at different time points in the monitoring of disease recurrence after radical bowel resection for primary colorectal cancer, the multi-gene methylation detection of peripheral plasma ctDNA was conducted before, after and during the postoperative follow-up period.	assessed up to 36 months
To establish a clinical cohort for colorectal cancer	It is expected that 800 patients with primary colorectal cancer diagnosed clinically will be enrolled for screening. Plasma samples 1-2 days before radical bowel resection will be collected for ColonAiQ polygene methylation test. Follow-up will be conducted 2 years after surgical resection, including CT/MRI imaging evaluation and blood CEA, etc. And dynamic monitoring of plasma ctDNA methylation level. Blood samples were collected for 9 times.	assessed up to 36 months

Collaborators and Investigators

• Sponsor: Singlera Genomics Inc.
• Collaborators: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Investigators: Principal Investigator: Rui Liu, Doctor, Singlera Genomics Inc.

Publications and helpful links

General Publications

• Pantel K, Alix-Panabieres C. Tumour microenvironment: informing on minimal residual disease in solid tumours. Nat Rev Clin Oncol. 2017 Jun;14(6):325-326. doi: 10.1038/nrclinonc.2017.53. Epub 2017 Apr 11. No abstract available.
• Young PE, Womeldorph CM, Johnson EK, Maykel JA, Brucher B, Stojadinovic A, Avital I, Nissan A, Steele SR. Early detection of colorectal cancer recurrence in patients undergoing surgery with curative intent: current status and challenges. J Cancer. 2014 Mar 15;5(4):262-71. doi: 10.7150/jca.7988. eCollection 2014.

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2022
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: June 25, 2022
• First Submitted That Met QC Criteria: July 1, 2022
• First Posted (Actual): July 6, 2022

Study Record Updates

• Last Update Posted (Actual): July 31, 2025
• Last Update Submitted That Met QC Criteria: July 28, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: ctDNA methylation; Recurrence monitoring
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Disease Attributes; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Recurrence; Colorectal Neoplasms
• Other Study ID Numbers: Protector-C

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No