Gut Microbiota, Hepatocellular Carcinoma, Organoids, Surgery, System Disorders, Digestive, Tumor Microenvironment
Conditions
Brief summary
A promising tool to elucidate the molecular characteristics of HCC are patient-derived organoids (PDOs), three-dimensional cultures of cells that self-organise according to tissue-specific patterns and can be used to test the susceptibility of a specific tumour to anticancer agents. In this study, PDOs for HCC will be developed that closely resemble the tumour microenvironment in vivo and mimic the crosstalk of the gut-liver axis to establish a correlation with patient prognosis and test the efficacy of available systemic therapies.
Detailed description
The objectives of the project will be 1) to develop HCC PDOs from tumour and non-tumour patient liver tissue obtained from surgical specimens or liver biopsies; 2) to evaluate genomic and transcriptomic changes resulting from the integration of HCC PDOs with patient-derived gut microbiota and host immune cells, and to assess the correlation with patient prognosis; 3) to exploit HCC PDOs to test the efficacy of systemic therapies (ICI and TKIs) and to understand possible modifying cofactors. Researchers with laboratory experience have been recruited who will focus on the construction of PDOs and the analysis of immune-inflammatory pathways. State-of-the-art technologies will be used, in particular next-generation sequencing, flow cytometry, high-throughput genomic and transcriptomic analysis, ultrafiltration, drug screening, multiplex immunoassays and enzyme immunoassays. The project aims to study the mechanisms involved in the modulation of therapeutic efficacy in patients with HCC. Therefore, the experimental model could be a valuable support to be integrated into real clinical practice to maximise therapeutic efficacy through a fully customised strategy.
Interventions
PROCEDUREorganoids models
Enrolled patients will undergo liver biopsy with sampling of tumor tissue and adjacent nontumor liver parenchyma. Alternatively, patients who are candidates for surgical resection of HCC will be enrolled. The tumor tissue obtained will be used partly for histological confirmation of HCC and then included in kerosene, partly used for organoid construction, and the nontumor tissue will be used solely for organoids. Genomic and transcriptomic changes resulting from the integration of PDO of HCC with the gut microbiota and host immune cells derived from the patient will be evaluated. In addition, PDOs from HCC will be tested for the efficacy of systemic therapies (ICI and TKI) and understand possible modifying co-factors.
Sponsors
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Capacity to express informed consent; * Age ≥18 years; * Suspected radiological diagnosis of HCC or diagnosis of HCC with indications for surgical resection.
Exclusion criteria
* Age \< 18 years; * Contraindications to liver biopsy (ascites, platelets\<50,000, INR\>1.7); * Contraindications to HCC resection surgery; * Active viral infection; * Refusal to sign informed consent to participate in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Organoid model development | 2-18 months | The primary endpoint of this study is to assess the correlation between the genomic and histological characteristics of patient-derived organoids (PDOs) from hepatocellular carcinoma (HCC) surgical biopsies and clinical outcomes, specifically disease-free survival (DFS) and overall survival (OS). |
Countries
Italy
Contacts
CONTACTFrancesca Romana Ponziani, PI
CONTACTElisabetta Creta, SC
PRINCIPAL_INVESTIGATORFrancesca Romana Ponziani, PI
Fondazione Policlinico A. Gemelli IRCCS, Rome, Largo A. Gemelli, 8
Outcome results
None listed