Decoding Epigenetic Mechanisms Driving Immune Evasion in Liver Cancer With Omics Approaches

NCT07432347 | Recruiting

• 1 other identifier: 6605
• Study Type: observational
• Target: 270
• Locations: 1 country
• Sites: 1

Brief Summary

This is a national, observational, retrospective, cross-sectional, non-profit study focused on patients with HCC. The study aims to characterize the expression and function of novel noncoding regulatory transcripts, including those containing TEsin the microenvironment of liver tumors, with emphasis on their role in T cell dysfunction.

Conditions

Hepatocarcinoma

Outcome Measures

Primary Outcomes (1)

• Characterize the molecular mechanisms underlying T cell dysfunction

  To characterize the molecular mechanisms underlying T cell dysfunction and immune evasion in the tumor microenvironment of hepatocellular carcinoma, through the identification and functional definition of novel non-coding regulatory transcripts - including those containing transposable elements - expressed at single-cell resolution. Identification of TE-containing transcripts expressed in tumor-infiltrating lymphocytes (TILs) and other cellular populations within the HCC tumor microenvironment, using single-cell transcriptomics (scRNA-seq) and spatial transcriptomics technologies.

  5 years

Secondary Outcomes (2)

• Analyze the epigenetic transcriptional regulatory mechanisms

  5 years

• Retrospective analysis on FFPE samples

  5 years

Study Arms (1)

HCC patients

120 patients will be prospectively recruitedand from whom fresh tumor samples and blood samples will be collected. 150 HCC patients treated by surgery FFPE samples will be retrospectively collected

Genetic: Collection of tumor tissue (Fresh or/and archival FFPE), blood samples

Interventions

Collection of tumor tissue (Fresh or/and archival FFPE), blood samples GENETIC

NGS, immunofluorescence analyses, transcriptional and immunophenotypic analyzes, scRNAseq, ChIP-seq/ATAC-seq, DNA methylation, single-cell transcriptomic and TCR sequencing

HCC patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with HCC and eligible for biopsy or surgical resection

1. Histological/radiological (LR-4 o 5)diagnosis of hepatocellular carcinoma (HCC). 2. Solid tumor fresh tissue availability from HCC biospy or surgical resectionas per standard clinical practice, and/orHCC FFPE archival samples availability. 3. Capability of understanding and signing an inform consent form. 4. Known hepatits B and C status, including HBeAg (positive or negative), viral load (HBVDNA e HCV-RNA), HCV genotype, whether sustained virological response (SVR)was obtainedand potential antiviral treatments received (including direct antiretroviral therapy(DAA)and interferon). These parameters will be exploited to stratify patients and analyze the impact of the virological status on microenvironmental immunological features, with particular regards to immunesuppression mechanisms.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Niguarda Hospital: lead
• San Raffaele University Hospital, Italy: collaborator
• Fondazione Istituto Nazionale Genetica Molecolare - INGM: collaborator
• University of Milan: collaborator

Study Sites (1)

ASST GOM Niguarda

Milan, Lombardy, 20162, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Tumor tissue (fresh and archival FFPE)

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Gianluca Mauri, MD

  ASST Grande Ospedale Metropolitano Niguarda

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gianluca Mauri, MD

CONTACT

+39026444; gianluca.mauri@ospedaleniguarda.it

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2026
• First Posted: February 25, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): January 31, 2029
• Study Completion (Estimated): January 31, 2031
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

IT (1)