Dissection of the Molecular and Immunological Interaction in Patients With HCC of Viral and Non-viral Etiologies

Study Overview
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Brief Summary
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This project will clarify the potential interaction between HBV infection and steatosis, and their impact on genetic alterations and tumor immune microenvironment.

Detailed Description
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This study will start with a training cohort of the NTUH and NTU Cancer Center patients, consisting of 4 sub-groups: HBV (+) steatosis (+), HBV (-) steatosis (+), HBV (+) steatosis (-) and HBV (-) steatosis (-). HBV (+) is defined as either: (a) HBsAg (+) or (b) HBsAg (-) anti-HBc (+) and HBV DNA detectable in blood or tumor tissue. Steatosis is defined by histology. We will enroll 400 patients who had sufficient tissue for testing in the training cohort. The following studies will be performed: (1) NGS of targeted genes panel using the National Health Research Institutes precision medicine platform; (2) transcriptomic analysis of immune microenvironment using RNA-seq and multiplex immunofluorescence staining; (3) lipotoxic genotyping for SNPs; (4) clinical outcomes of MAFLD vs. non-MAFLD. The genetic and immunological features will be further tested by a validation cohort, from collaborative hospitals. This project will clarify the potential interaction between HBV infection and steatosis, and their impact on genetic alterations and tumor immune microenvironment.

Official Title
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Dissection of the Molecular and Immunological Interaction in Patients With Hepatocellular Carcinoma of Viral and Non-viral Etiologies

Conditions
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Hepatocellular Carcinoma

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult female or male patients aged ≥20 years. HCC has been histologically confirmed with resection specimen. The surgery should be performed with curative intent after 2015 in the study hospital. Availability of serum HBsAg and Anti-HBc data in the electronic medical record. Availability of imaging data performed within 3 months before the surgery in the electronic medical record. (at least one of the following: computed tomography, magnetic resonance imaging, abdominal sonography). Informed consent is obtained. Willingness to provide the residual operative slides and medical records. Exclusion Criteria: Fibrolamellar HCC, sarcomatoid HCC, or a mixture of cholangiocarcinoma and HCC Exclusion of HCV patients (Anti-HCV positive) Inability to cooperate by providing a complete medical history.

Ages Eligible for Study
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Minimum Age: 20 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 |
| --- | --- |
| training cohort<br>Consisting of 4 sub-groups: HBV (+) steatosis (+), HBV (-) steatosis (+), HBV (+) steatosis (-) and HBV (-) steatosis (-). HBV (+) is defined as either: (a) HBsAg (+) or (b) HBsAg (-) anti-HBc (+) and HBV DNA detectable in blood or tumor tissue. Steatosis is defined by histology. We will enroll 400 patients who had sufficient tissue for testing in the training cohort. | |
| validation cohort<br>For the validation cohort, the clinical and pathological information will be obtained retrospectively by TCOG and will take 6 months to identify eligible patients for the 4 sub-groups listed above. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| transcriptomic analysis of immune microenvironment | using RNA-seq and multiplex immunofluorescence staining | 2 Years | 
| lipotoxic genotyping for SNPs | lipotoxic genotyping for SNPs | 2 years | 
| clinical outcomes of MAFLD vs. non-MAFLD. | clinical outcomes of MAFLD vs. non-MAFLD. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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next-generation sequencing, precision medicine, Hepatocellular Carcinoma