Auxiliary Diagnosis of Liver Nodules Using cfDNA Whole-genome Signatures

Study Overview
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Brief Summary
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As a prospective, multi-center study, GUIDER will recruit 400 liver nodules participants from different provinces and regions across China. Except for cfDNA signatures, serum biomarkers, histopathological biopsy and enhanced MRI will also be performed. The sensitivity and specificity of the cfDNA signature based-model in liver nodules diagnosing will be evaluated.

Detailed Description
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Patients with liver nodules will be recruited for 1 year. Peripheral blood samples of all participants will be collected after being informed about the study and potential risks. CfDNA extraction, library construction, and whole genome sequencing will be performed. A machine learning method will be implemented for cfDNA signatures-based model construction at the end of the study. Sensitivity and specificity will be used to evaluate the performance of cfDNA signatures-based model in liver nodules diagnosis.

Official Title
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Auxiliary Diagnosis of Liver Nodules Using cfDNA Whole-genome SignatuRes (GUDIER): an Observational Cohort Trial

Conditions
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Focal Liver Lesions

Intervention / Treatment
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* Other: No interventions


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eighteen years or elder； Participants underwent enhanced MRI for the evaluation of liver nodules ≤5 cm； Participants whose platelet count ≥ 50×109/L, prothrombin activity (PTA) ≥ 60%； Participants who are willing and able to perform hepatectomy or tissure biopsy. Exclusion Criteria: Participants with different enhancement mode liver nodules that detected by enhanced MRI and without CEUS confirmation； Diagnosis of malignant tumors before recruitment； Anti-tumor therapy before recruitment ； HIV infection； Pregnancy； Allogenic blood transfusion or cell therapy within 14 days before peripheral blood samples collection; Participants with hepatic encephalopathy, hemangioma, ascites, gastrointestinal bleeding, jaundice, liver failure, congestive heart failure, or any other serious diseases that causing organ damage. Participants with any other factors that may leading to termination of the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Malignant liver nodules cohort<br>Participants with malignant liver nodules diagnosed by pathological biopsy. | Other: No interventions<br>* No interventions<br>|
| Benign liver nodules cohort<br>Participants with benign liver nodules diagnosed by pathological biopsy or imaging examination. | Other: No interventions<br>* No interventions<br>|
| Uncertain benign or malignant liver nodules cohort<br>Participants with liver nodules could not be diagnosed definitely by imaging examination and serum protein markers. | Other: No interventions<br>* No interventions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of the cfDNA whole-genome signatures based model in liver nodules diagnosis. | Sensitivity is defined as the ratio of positively detected participants in all malignant nodule patients by cfDNA signatures. | Enrollment of the first participant up to 18 months | 
| Specificity of the cfDNA whole-genome signatures based model in liver nodules diagnosis. | Specificity is defined as the proportion of negatively detected participants in all benign liver nodules patients by cfDNA signatures. | Enrollment of the first participant up to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Specificity of the model that composed of cfDNA signatures, imaging examination，serum protein markers and clinical characteristics in liver nodules diagnosis. | Specificity is defined as the proportion of negatively detected participants in all benign liver nodules patients by the model that composed of cfDNA whole-genome signatures, imaging examination，serum protein markers， and clinical characteristics. | Through study completion，an average of 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatocellular carcinoma, liquid biopsy, peripheral blood, cfDNA, liver nodules, auxiliary diagnosis