Hepatocellular Carcinoma
Conditions
Brief summary
The goal of this interventional study is to create hepatocellular carcinoma organoids from liver bioptic samples of individuals with hepatocellular carcinoma. The main questions it aims to answer are: * the feasibility of hepatocellular carcinoma organoids integrated with host gut microbiota and peripheral blood mononuclear cells * the molecular pattern of the organoid tumor microenvironment * the in vitro therapeutic response of hepatocellular carcinoma organoids
Interventions
PROCEDURELiver biopsy
The liver biopsy is ultrasound-guided and target the hepatic lesions. It is performed with 18G or 19G Menghini needle. A part of bioptic sample will be used for genomic analysis. An other part of sample will be cultured to create the organoid. The organoid's cultures will be integrated with the host gut microbiota (collected by a fecal sample) and peripheral blood mononuclear cells (from venous blood sample) and they will be used for research such as molecular analysis and pharmacological tests.
Sponsors
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ability to express informed consent * Patients ≥ 18 years of age * Radiological diagnosis of hepatocellular carcinoma (HCC)
Exclusion criteria
* Patients \<18 years of age * Contraindications for liver biopsy: ascites, platelet count \<50.000, International Normalized Ratio (INR) \>1.7 * Active viral infection * Refusal to give informed consent for the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Success rate of hepatocellular carcinoma organoids integrated with host gut microbiota and peripheral blood mononuclear cells | within 12 months | Number of successfully created organoids from all hepatocellular carcinoma samples |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Analysis of hepatocellular carcinoma organoid transcriptome distribution within a reference set from The Cancer Genome Atlas | within 12 months | Comparison between organoids transcriptome and data from The Cancer Genome Atlas |
| Evaluation of the concordance of somatic genetic mutations between the organoid and the original tumor | within 12 months | DNA organoids and original tumor sample sequencing and comparison between the somatic genetic mutations found in both models |
| Correlation between gut microbiota community profiling and growth rate of hepatocellular carcinoma organoids | within 12 months | Definition of microbiota composition via DNA and RNA sequencing and correlation between specific bacteria abundance and successful organoids growth |
| Treatment response evaluation in vitro | Day 5 | Evaluation of organoids' tumor cells survival after 5 days of chemotherapy treatment. Treatment will include different concentrations of sorafenib, lenvatinib, atezolizumab, bevacizumab, tremelimumab, durvalumab, regorafenib, cabozantinib. Tumor cells vitality will be assessed trough Cell TitelGlo3D Cell Viability Assay. |
Countries
Italy
Outcome results
None listed