A Study on a Blood-based Dual-target Test for CRC Detection

Study Overview
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Brief Summary
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To evaluate the effectiveness and accuracy of the ctDNA dual-target test kit in a large case-control cohort for the detection of colorectal cancer and advanced adenomas.

Detailed Description
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Usually, colorectal cancers (CRCs) diagnosed in their early stages are curable, especially precancerous lesions (adenomas, polyps) that can be removed during a colonoscopy.However, due to low patient compliance and limited resources, colonoscopy is not feasible for screening the average-risk population. gFOBT/FIT are limited by their low sensitivity and high false-positive rate. Compared to colonoscopy and stool DNA tests, blood-based methylation tests showed greater patient compliance and convenience. Hypermethylated NTMT1 and MAP3K14-AS1 were found in multiple cohorts of CRC samples in our previous study. In this study, we aimed to evaluate the effectiveness and accuracy of the ctDNA dual-target(NTMT1 and MAP3K14-AS1) test kit in 5 tertiary hospitals around china for the detection of colorectal cancer and advanced adenomas. Fecal immunochemical test (FIT) will also privided to participants in the study. Sanger sequencing would be performed to evalute the accuracy of the dual-target methylation detection test kit.

Official Title
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Validation of a ctDNA Methylation-based Dual-target Test for the Detection of Colorectal Cancer: a Multicenter Clinical Study

Conditions
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Colorectal Cancer, Colorectal Adenoma

Intervention / Treatment
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* Diagnostic Test: Test of methylated NTMT1 and MAP3K14-AS1
* Diagnostic Test: FIT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion Criteria for CRC group（≥30%） 1)Patients with colorectal cancer 2)Follow-up sample subjects: Subjects who underwent resection of colorectal cancer lesions. Inclusion Criteria for Control group（≤70%） Health volunteer, or subject with other diseases or physiological conditions other than colorectal cancer, including but not limited to gastritis, gastric cancer, esophagitis, rheumatoid arthritis, prostate cancer, microbes (inflammation patients), gastrointestinal bleeding, drugs (typical digestive tract medication) Population), neuroendocrine cancer, squamous cell carcinoma (squamous squamous cell carcinoma, esophageal squamous cell carcinoma); Exclusion Criteria: Patients who had undergone radical resection of bowel cancer (except for postoperative follow-up) and those who had received anti-tumor therapy such as radiotherapy/chemotherapy； Colorectal cancer or colorectal adenoma with other malignancies； Postoperative follow-up patients of colorectal cance with distant metastasis; The sample size collected did not meet the detection requirements; Other patients who are considered unsuitable for this study (such as pregnancy, high blood pressure, heart disease, etc., who are not suitable for colonoscopy due to physical condition).
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CRC group<br>patients with colorectal cancer | Diagnostic Test: Test of methylated NTMT1 and MAP3K14-AS1<br>* A dual-target test kit to detect methylated NTMT1 and MAP3K14-AS1 in blood samples.<br>Diagnostic Test: FIT<br>* Fecal immunochemical test（optional）<br>|
| Control group<br>patients without olorectal cancer | Diagnostic Test: Test of methylated NTMT1 and MAP3K14-AS1<br>* A dual-target test kit to detect methylated NTMT1 and MAP3K14-AS1 in blood samples.<br>Diagnostic Test: FIT<br>* Fecal immunochemical test（optional）<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity | Sensitivity (for CRC and\or advanced precancerous neoplasm) of this blood-based methylation dual-target test. A diagnostic colonoscopy procedure is the reference method. Lesions will be confirmed as malignant or precancerous by histopathologic examination. Other clinically acceptable diagnostic criteria for non-intestinal diseases. | Through study completion, an average of 1 year. | 
| Specificity | Specificity (for CRC and\or advanced precancerous neoplasm) of this blood-based methylation dual-target test. A diagnostic colonoscopy procedure is the reference method. Lesions will be confirmed as malignant or precancerous by histopathologic examination. Other clinically acceptable diagnostic criteria for non-intestinal diseases. | Through study completion, an average of 1 year. | 
| Accuracy | Accuracy of the kit for methylation detection. Validation of the methylation status of MTNT1 and MAP3K14-AS1 by Sanger sequencing. | Through study completion, an average of 1 year. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined sensitivity | Sensitivity when combined the blood-based methylation dual-target test with FIT | Through study completion, an average of 1 year. | 
| Combined specificity | Specificity when combined the blood-based methylation dual-target test with FIT | Through study completion, an average of 1 year. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ctDNA, Methylation, Diagnostic test