Non-invasive Auxiliary Diagnosis of Colorectal Cancer and Advanced Adenoma by Detecting Cancer-specific Methylation Signatures in Plasma ctDNA
Trial Snapshot
- Phase
- Not Applicable
- Sponsor
- Enrollment
- 1,300
- Locations
- 1
- Primary Endpoint
- Assay sensitivity and specificity for colorectal cancer and advanced adenoma
Study Overview
Brief Summary
Colorectal cancer is a common malignant tumor of the digestive tract. It is still a challenging task to detect colorectal cancer at an early stage. Studies have found that DNA methylation has a relationship with the occurrence and development of tumors. Singlera Genomics Inc. has invented the proprietary methyl-Titan sequencing technology and developed a detection method for colorectal cancer and advanced adenoma (Adenoma/Colorectal cancer Early detection, ACE) using the cancer-specific methylation markers. ACE is a blood-based non-invasive diagnostic technique. It has high compliance rate compared with colonoscopy, and sampling is more convenient than stool testing. It also has much higher sensitivity compared to existing blood testing methods.
The current study plans to use ACE method to analyze ctDNA in the blood for the cancer-specific DNA methylation markers to aid in the differential diagnosis of patients with colorectal cancer or adenoma. This technique will greatly reduce the discomfort in the diagnosis of suspected patients and improve the diagnosis of high-risk population of colorectal cancer.
The goals of this study are: 1) to establish a detection system based on plasma ctDNA methylation sequencing technology for the auxiliary diagnosis of colorectal cancer and adenoma, 2) to assess the diagnostic value of plasma ctDNA methylation signature for colorectal cancer and adenoma, and 3) to assess the association of plasma ctDNA methylation signals with colonoscopy results and pathological results of surgical specimens.
A total of 1300 patients (700 cases positive and 600 cases negative) aging between 45 and 80 years old will be enrolled. Colonoscopy will be performed to determine whether patients are positive or negative. Positive patients who need surgical resection will be further classified according to their surgical histopathological results. For negative patients, the type of lesion will be clarified. The plasma samples of all subjects will be analyzed for cancer-specific ctDNA methylation profiles. Based on the results of plasma ctDNA methylation test, the risks of colorectal cancer of the enrolled subjects are scored. Combined with the grouping information, the clinical application value of the cancer-specific methylation profile for early cancer diagnosis will be assessed.
Detailed Description
- Research Background
1.1 Diagnosis of colorectal cancer Colorectal cancer is a common malignant tumor of the digestive tract. According to statistics from 2015, both morbidity and mortality of colorectal cancer in China are among the top five of all cancers. Studies have shown that the five-year survival rate of patients can achieve 90% if patients are diagnosed before the spread of tumor cells. However only 40% of patients are currently diagnosed at early stage. Therefore, treatment in the early stage of the disease is a necessary means to cope with colorectal cancer. The main method used clinically for diagnosis is colonoscopy. This method is accurate, but limited by many factors, such as diarrhea, intestinal perforation, and need to be prepared in many ways before the examination. The patients need to eat fluid diet, clean the intestines, etc. Other diagnostic methods such as imaging, histopathological examination have a low detection rate, or cause damage to the organ. Therefore, it is a still challenging task to detect colorectal cancer at an early stage.
1.2 Detection of ctDNA methylation in colorectal cancer patients and clinical studies Epigenetics refers to a heritable phenotypic change without a change in the primary sequence of the DNA. DNA methylation is one of the epigenetic modification pathways, which can cause changes in chromatin structure and DNA stability, and regulate gene transcription and expression. Studies have found that DNA methylation has an close relationship with the occurrence and development of tumors. DNA methylation changes occur at numerous sites of DNA in tumor cells as compared to normal cells. Further studies show that DNA methylation occur early in the process of cancer, making it possible to use DNA methylation for early screening of cancer.
Based on the research paper published by professor Kun Zhang in Nature Genetics, Singlera Genomics Inc. invented the proprietary methyl-Titan sequencing technology and developed a detection method for colorectal cancer and advanced adenoma (Adenoma/Colorectal cancer Early detection, ACE). ACE is a blood-based non-invasive diagnostic technique. It has high compliance rate compared with colonoscopy, and sampling is more convenient than stool testing. It also has much higher sensitivity compared to existing blood testing methods. Based on these advantages, the ACE technology is suitable for early colorectal cancer diagnosis.
During the development stage Singlera Genomics Inc. used a high-throughput and high-coverage screening method for 4 million CpG methylation sites in the genome, and analyzed different stages of colorectal cancer, adenoma, polyp tissue samples and paired normal tissues to screen colorectal cancer-related methylation sites. Plasma samples from cancer patients and healthy people were also analyzed to select ctDNA methylation markers for colorectal cancer.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 45 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Age 45~80 years old, gender is not limited, women are not in pregnancy and lactation;
- •Willing to accept a full colonoscopy;
- •The patients enrolled are newly diagnosed patients who did not receive surgery, radiotherapy, chemotherapy, targeted therapy or other tumor-related intervention;
- •The anticoagulant drugs such as warfarin, aspirin and Plavix were stopped for 1 week, and low molecular weight heparin was stopped on the same day;
- •No history of other cancer diseases, normal liver and kidney function;
- •No major trauma requiring blood transfusion treatment occurred within one week.
Exclusion Criteria
- •Have had colorectal cancer or intestinal adenoma before;
- •Have other cancer history;
- •Previously undergoing a colon and rectal resection (except for sigmoid diverticulosis);
- •Patients with Lynch syndrome in the family;
- •History of severe cardiovascular disease (eg previous myocardial infarction, coronary artery bypass grafting or coronary stenting, history of congestive heart failure; myocardial infarction within 6 months, uncontrolled severe hypertension, etc.), or patients that the investigator determines not suitable for enrollment;
- •Participated in "interventional" clinical trials and have taken test drugs over the past 30 days;
- •Patients that the investigator determines not suitable for enrollment;
- •Failure to follow the test plan to collect blood on time;
- •The blood collection sample does not meet the requirements.
Outcomes
Primary Outcomes
Assay sensitivity and specificity for colorectal cancer and advanced adenoma
Time Frame: August 17, 2018- September 30, 2020
Assay sensitivity and specificity will be determined using colonoscopy and histopathological results as the gold standard. The following formula will be used to calculate sensitivity and specificity: sensitivity= TP/(TP+FN); specificity= TN/(TN+FP)
Secondary Outcomes
No secondary outcomes reported
Investigators
Pinghong Zhou
Director of Endoscopy Center
Shanghai Zhongshan Hospital