Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06134973 |
| Other study ID # |
Fangwang03 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
September 1, 2023 |
| Est. completion date |
June 2025 |
Study information
| Verified date |
November 2023 |
| Source |
Tianjin Third Central Hospital |
| Contact |
Fengmei Wang, PhD |
| Phone |
15522242696 |
| Email |
wangfengmeitj[@]126.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
Liquid biopsy technology based on high-throughput sequencing can detect trace signals in the
early stage of cancer in plasma free DNA, so it has become a new technology suitable for
tumor diagnosis and screening.Relying on the key discipline of digestive liver disease in our
hospital, this project cooperated with BGI to jointly carry out a prospective study on the
application of liquid biopsy in the monitoring of population at risk of liver cancer by
taking advantage of its technical advantages in next-generation sequencing, so as to provide
an innovative way for the prevention and treatment of Hepatocellular Carcinoma.
Description:
Hepatocellular Carcinoma (HCC)is one of the cancers with high morbidity and mortality in the
world , and the incidence of liver cancer in China is particularly serious. In 2020, there
will be 410,000 new cases of liver cancer in China, accounting for 42.5% of the world. There
were 391,000 deaths, ranking fifth in the incidence of malignant tumors and second in the
fatality rate . Most patients with primary liver cancer have insidious onset and have reached
the middle and late stage when diagnosed. At this time, the treatment of liver cancer is few,
the prognosis is poor, and the mortality is high.Early detection and treatment are of great
significance to improve the survival rate of patients with liver cancer, and the 5-year
survival rate after early liver cancer (BCLC stage 0/A) can reach more than 60%. However, the
diagnosis rate of early liver cancer in China is only 30%. In other countries, early
diagnosis rates can be increased to more than 60% by monitoring high-risk populations. It can
be seen that close monitoring of the pre-cancer stage is the key to early diagnosis and early
treatment of HCC.
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.
