A Prospective Study on the Application of Liquid Biopsy in the Surveillance of High-risk Population of HCC.
NCT ID: NCT06134973
Last Updated: 2023-11-22
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
1000 participants
OBSERVATIONAL
2023-09-01
2025-06-30
Brief Summary
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Detailed Description
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Identifying people at high risk for cancer development is the premise of cancer Surveillance and the biggest difference from conducting tumor Screening in the general population. Compared with many other common cancers, Targets for liquid biopsies come in many forms, including genetics-based tests for gene mutations, and epigenetic-based tests for methylation. Since no specific gene mutation events directly related to cancerization have been found in liver cancer, the effect of searching for biomarkers along this route is limited. Therefore, detecting early liver cancer from the epigenetic level has become another way worth exploring.
In the epigenetic mechanism, DNA methylation is an important gene regulation mode, which is closely related to the occurrence and development of tumors. More importantly, abnormal methylation of cancer-related genes often occurs in the early stage of cancer development, so DNA methylation signals are considered as potential markers for early tumor screening \[14\]. In addition, methylation modification is tissue-specific in different tumors and can even be used to locate the primary tissue of cancer, which is an ideal molecular marker for tumor early screening \[15\]. Therefore, ctDNA, which carries tumor cell-specific methylation information, can be used as a target for liquid biopsy of liver cancer, providing an innovative path for early diagnosis of HCC develops gradually on the basis of clear causes, such as typical hepatitis, cirrhosis to liver cancer "three steps". These characteristics determine the target population for early diagnosis of HCC, which can be found in the medical treatment of various chronic liver diseases. Making full use of these precancerous risk factors and identifying high-risk groups of liver cancer as surveillance objects will help improve the detection rate of cancer and obtain a better benefit-cost ratio.
Intrahepatic nodules are the disorder of hepatic trabecular arrangement caused by fibrous tissue hyperplasia. Their formation indicates the progression of liver injury and is also an important stage of precancerous lesions. Pathologically, nodules can be divided into stages such as regenerated nodules, low grade and high grade atypical hyperplasia, and adenoma according to their proximity to cancer, but the standards and terminology are still difficult to be unified, and pathological diagnosis requires obtaining samples through liver puncture, which is not widely used in clinical practice. In this case, the size of the intrahepatic nodules detected by ultrasound becomes an important basis for liver cancer risk stratification. Taking the current guidelines for diagnosis and treatment of liver cancer in China as an example, whether the nodule diameter is greater than 2 cm is the main basis for classification and diagnosis: for nodules less than 2 cm, at least two imaging evidences are required to confirm liver cancer; For nodules larger than 2 cm, only one item is needed. In addition, stratified analysis based on the size of intrahepatic nodules is also a framework for objective evaluation of the role of tumor markers. Alpha-fetoprotein (AFP), a traditional serum marker for hepatocellular carcinoma, has a sensitivity of 72-87% in advanced hepatocellular carcinoma. But for early-stage liver cancer smaller than 2 cm, its sensitivity is only 30-50%.
In view of the shortcomings of traditional serological markers with few types and low specificity, many important advances have been made in the application of molecular detection techniques based on omics to cancer diagnosis and screening. The liquid biopsy technology based on high throughput sequencing can detect specific abnormal signals in a small amount of Circulating Tumor DNA (ctDNA) in human peripheral blood, thus promoting the technological innovation of tumor early screening.
Targets for liquid biopsies come in many forms, including genetics-based tests for gene mutations, and epigenetic-based tests for methylation. Since no specific gene mutation events directly related to cancerization have been found in liver cancer, the effect of searching for biomarkers along this route is limited. Therefore, detecting early liver cancer from the epigenetic level has become another way worth exploring.
In the epigenetic mechanism, DNA methylation is an important gene regulation mode, which is closely related to the occurrence and development of tumors. More importantly, abnormal methylation of cancer-related genes often occurs in the early stage of cancer development, so DNA methylation signals are considered as potential markers for early tumor screening . In addition, methylation modification is tissue-specific in different tumors and can even be used to locate the primary tissue of cancer, which is an ideal molecular marker for tumor early screening . Therefore, ctDNA, which carries tumor cell-specific methylation information, can be used as a target for liquid biopsy of liver cancer, providing an innovative path for early diagnosis of HCC.
Although liquid biopsy shows promising application in the early diagnosis of HCC, most results are based on retrospective studies. According to the steps of marker research and development, future and multi-center studies are needed to verify it. In this project, we will rely on the team and work foundation of the key discipline of digestion (Liver disease), and cooperate with BGI Shenzhen BGI Medical Laboratory to carry out liquid biopsy based on methylation, and evaluate its feasibility for liver cancer monitoring through prospective studies. Promote the realization of early detection, diagnosis and treatment of HCC.
The risk assessment model of liver cancer was established to identify the high-risk groups of liver cancer. A prospective cohort study was conducted to evaluate the predictive ability of liquid biopsy technology for liver cancer occurrence, and to verify the performance and application prospects of this novel genetic detection technology in liver cancer monitoring.
Conditions
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Study Design
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COHORT
PROSPECTIVE
Study Groups
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Nodular group
nodules less than 2 cm in diameter
ultrasonic testing
ultrasonic testing
Macronodular group
nodules between 2-3 cm in diameter
ultrasonic testing
ultrasonic testing
Interventions
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ultrasonic testing
ultrasonic testing
Eligibility Criteria
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Inclusion Criteria
2. Intrahepatic nodules detectable by ultrasound;
3. Unlimited number of nodules;
4. The patient has signed an informed consent form.
Exclusion Criteria
2. Patients who are unable to cooperate with venous blood sampling；
3. According to the judgment of the investigator, the participants are not suitable to participate in this study.
18 Years
ALL
No
Sponsors
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BGI, China
OTHER
Tianjin Third Central Hospital
OTHER
Responsible Party
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Principal Investigators
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Fengmei Wang, PhD
Role: PRINCIPAL_INVESTIGATOR
Tianjin Third Central Hospital
Locations
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王芳
Tianjin, Tianjin Municipality, China
Countries
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Central Contacts
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Facility Contacts
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Other Identifiers
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Fangwang03
Identifier Type: -
Identifier Source: org_study_id