Establishment of a Clinical Diagnostic Model GAMAD for Early-stage HCC Based on Circulating Tumor DNA Methylation
Study Details
Study Description
Brief Summary
Most hepatocellular carcinoma (HCC) cases were at advanced stage when diagnosis established. This study is intended to establish a clinical diagnostic model GAMAD for early-stage HCC and evaluate the diagnostic efficiency the same time. This study is a multicenter case control study. Participants including healthy control,HCC, liver cirrhosis, hepatitis and benign tumor-like lesions are consecutively recruited into the cohort. All the blood samples are collected before any treatments and will be tested in single center in order to decrease bias.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
GALAD score including age, sex, PIVKA-II(DCP), Alpha-fetoprotein (AFP) and alpha-fetoprotein L3 (AFP-L3), is a serum biomarker-based panel that can aid in early detection among patients with a high risk for liver cancer. While increasing studies showed the diagnostic accuracy of AFP-L3 was not as good as that of AFP or PIVKA-II, and AFP-L3 was not significant in the multivariable model. Thus, a model with better diagnostic accuracy and more suitable for Chinese patients is needed. Here, based on a multi-locus blood-based assay targeting circulating tumor DNA methylation, we aim to develop a novel diagnostic model--GAMAD (gender, age, mythylation, AFP and DCP) and validate its performance among HCC patients and those at high risk of developing HCC,such as liver cirrhosis, hepatitis patients. This is a multicenter, observational, case control study. After giving fully informed consent, the participants will undergo the regular treatment according to NCCN guidelines.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Hepatocellular Carcinoma patients Blood samples are collected before liver resection. |
Diagnostic Test: GAMAD
Blood samples are tested for tumor markers including PIVKA-II (DCP),AFP, ctDNA methylation and biochemical tests.
|
| Liver cirrhosis The diagnosis of liver cirrhosis are based on triple-phase contrast enhanced computed tomography, magnetic resonance imaging. |
Diagnostic Test: GAMAD
Blood samples are tested for tumor markers including PIVKA-II (DCP),AFP, ctDNA methylation and biochemical tests.
|
| Hepatitis Patients with various hapatitis. |
Diagnostic Test: GAMAD
Blood samples are tested for tumor markers including PIVKA-II (DCP),AFP, ctDNA methylation and biochemical tests.
|
| Benign tumor-like lesions Benign hepatic tumors were diagnosed based on imaging findings and histological examinations after hepatic resection. |
Diagnostic Test: GAMAD
Blood samples are tested for tumor markers including PIVKA-II (DCP),AFP, ctDNA methylation and biochemical tests.
|
| Healthy control The healthy control group consist of people undergoing routine medical examination. Blood samples are collected. |
Diagnostic Test: GAMAD
Blood samples are tested for tumor markers including PIVKA-II (DCP),AFP, ctDNA methylation and biochemical tests.
|
Outcome Measures
Primary Outcome Measures
- GAMAD [Day one]
Using GAMAD calculator model to obtain the score of each group.
Secondary Outcome Measures
- GALAD [Day one]
Using GALAD calculator to obtain the score of each group.
- circulating tumor DNA methylation [Day one]
Using circulating tumor DNA methylation to obtain diagnostic value in pre-specified subgroups.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age above 18
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Establishing Diagnosis according to the European Association for the Study of Liver(EASL) criteria
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High risk group of developing HCC including liver cirrhosis and hepatitis under the confirmed diagnosis
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Able to provide sufficient and qualified blood samples for study tests
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No prior or undergoing cancer treatment (local or systematic)
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Able to provide a written informed consent
Exclusion Criteria:
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Obstructive jaundice patients
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Medical history of taking warfarin
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With other known malignant tumors or multiple primary tumors
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Patients with autoimmune diseases, genetic diseases, mental diseases/ disabilities and other diseases considered unsuitable for the study by the investigator
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During pregnancy or lactation
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Recipient of blood transfusion within 3 months prior to study blood draw
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Insufficient qualified blood sample for study test
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Singlera Genomics Inc.
- The First Hospital of Jilin University
Investigators
- Study Director: Guoyue Lv, Ph.D, The First Hospital of Jilin University
- Principal Investigator: Guoyue Lv, Ph.D, The First Hospital of Jilin University
Study Documents (Full-Text)
None provided.More Information
Publications
- Liu S, Sun L, Yao L, Zhu H, Diao Y, Wang M, Xing H, Lau WY, Guan M, Pawlik TM, Shen F, Xu M, Tong X, Yang T. Diagnostic Performance of AFP, AFP-L3, or PIVKA-II for Hepatitis C Virus-Associated Hepatocellular Carcinoma: A Multicenter Analysis. J Clin Med. 2022 Aug 29;11(17):5075. doi: 10.3390/jcm11175075.
- Yang T, Xing H, Wang G, Wang N, Liu M, Yan C, Li H, Wei L, Li S, Fan Z, Shi M, Chen W, Cai S, Pawlik TM, Soh A, Beshiri A, Lau WY, Wu M, Zheng Y, Shen F. A Novel Online Calculator Based on Serum Biomarkers to Detect Hepatocellular Carcinoma among Patients with Hepatitis B. Clin Chem. 2019 Dec;65(12):1543-1553. doi: 10.1373/clinchem.2019.308965. Epub 2019 Oct 31.
- GAMAD