NCT07100236

29-Gene Liver Cancer Subtype and Immunotherapy Effectiveness

Identification of a Novel 29-Gene-Based Subtype of Hepatocellular Carcinoma and Its Correlation With Immunotherapy Efficacy

• Status: Not Yet Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 350 (estimated)
• Sponsor: Junjie Xu · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This clinical study plans to include 350 liver cancer patients from 10 tertiary hospitals nationwide, starting from August 1, 2025, at multiple centers such as the affiliated Run Run Shaw Hospital of Zhejiang University School of Medicine (the leading unit). They will be divided into a new typing queue (100 cases) and another typing queue (250 cases) using the 29 gene set algorithm. The study will collect tumor tissue samples obtained from surgical resection or puncture of patients (meeting the requirements of sample size and tumor cell proportion), perform RNA seq transcriptome sequencing, and extract patient baseline data, clinical pathological characteristics, laboratory test results, treatment information, and follow-up data from the hospital medical record system. The main objective of this study is to observe the disease progression time (TTP) and objective response rate (ORR) of patients after receiving targeted combined immunotherapy. The secondary observations include progression free survival (PFS), overall survival (OS), dynamic changes in tumor markers, liver function status, and survival after progression. The aim is to analyze the correlation between the 29 gene based new subtype of liver cancer and the efficacy of immunotherapy, providing a basis for precise diagnosis and treatment of liver cancer.

Detailed description

This is a multicenter cohort study aimed at exploring the correlation between a novel 29-gene-based subtype of primary hepatocellular carcinoma (HCC) and response to immunotherapy, with the goal of verifying that this new subtype exhibits higher responsiveness to immunotherapy. Study Population: A total of 350 patients with pathologically confirmed primary HCC will be enrolled from 10 tertiary hospitals across China, with Sir Run Run Shaw Hospital, Zhejiang University School of Medicine as the leading center. Eligibility criteria include: age ≥ 18 years; having measurable tumor lesions per RECIST 1.1; receiving targeted therapy combined with immune checkpoint inhibitors (ICI) after sample collection (with ≥4 weeks interval from prior local treatments if any); availability of qualified tumor samples (≥3g frozen surgical tissues or biopsy specimens sufficient for transcriptome sequencing); and provision of informed consent. Patients will be excluded if they have overlapping local treatments (e.g., TACE, ablation, radiotherapy) during or within 4 weeks of target-ICI combination therapy, concurrent active malignancies (except cured basal cell carcinoma, etc.), severe organ dysfunction (e.g., Child-Pugh Class C liver function, NYHA Class Ⅲ-Ⅳ cardiac function), or other factors interfering with efficacy assessment as judged by investigators. Study Procedures: Sample Processing and Subtyping: Tumor samples will undergo RNA sequencing using the Illumina HiSeq platform (outsourced to Hangzhou DIAN Diagnostics company). After quality control, alignment, and quantification, hierarchical clustering based on a 29-gene signature will classify patients into a "novel subtype cohort" (unmatchable to TCGA HCC clusters) and an "other subtypes cohort". Data Collection: Clinical data will be extracted from electronic medical records, including baseline characteristics (age, gender, Child-Pugh classification), treatment details (target-ICI regimens, doses, cycles), imaging evaluations (enhanced CT/MRI for tumor response assessment per mRECIST), and follow-up data (survival status, tumor marker dynamics). Outcome Measures: Primary Outcomes: Time to Progression (TTP, defined as the interval from initiation of target-ICI therapy to first progression per mRECIST) and Objective Response Rate (ORR, proportion of patients achieving complete response \[CR, disappearance of arterial enhancement in all target lesions\] or partial response \[PR, ≥30% reduction in sum of target lesion diameters\]). ORR will be assessed at Weeks 8, 16, 24, or progression for each line of therapy; if regimens are changed due to poor efficacy, assessment timelines will be reset for the new regimen, with CR/PR status strictly linked to the corresponding regimen. Secondary Outcomes: Progression-Free Survival (PFS), Overall Survival (OS), dynamic changes in tumor markers (AFP, PIVKA-II), liver function status at progression, and Post-Progression Survival (PPS). Statistical Analysis: Group differences will be compared using appropriate tests (t-test, ANOVA, Mann-Whitney U test, Chi-square test, or Fisher's exact test as applicable). Survival analyses (TTP, PFS, OS, PPS) will employ the Kaplan-Meier method with Log-rank tests, and Cox proportional hazards models will evaluate the impact of 29-gene subtyping on progression risk. A p-value \< 0.05 will be considered statistically significant. This study aims to provide evidence for precision immunotherapy in HCC by clarifying the association between the 29-gene-based subtype and immunotherapeutic efficacy.

Conditions

• Primary Hepatocellular Carcinoma

Interventions

Type	Name	Description
OTHER	Observational study of 29 - gene - defined HCC subtypes and immunotherapy responsiveness correlation	This is a non - interventional observational study. We will stratify patients with hepatocellular carcinoma (HCC) based on transcriptome sequencing of their tumor samples, specifically using a 29 - gene signature to classify them into different subtypes. Without interfering with patients' existing immunotherapy regimens (which are determined by clinical practice), we will retrospectively collect and analyze data on treatment responses. The goal is to explore the correlation between the 29 - gene - based HCC subtypes and responsiveness to immunotherapy, focusing on differences in outcomes like objective response rate (ORR) and progression - free survival (PFS) across subtypes. This study distinguishes itself by emphasizing observational analysis of pre - existing treatment patterns rather than implementing active interventions, aiming to provide insights into personalized immunotherapy for HCC through genetic subtyping.

Timeline

• Start date: 2025-08-01
• Primary completion: 2027-05-01
• Completion: 2027-08-01
• First posted: 2025-08-03
• Last updated: 2025-08-03

Locations

13 sites across 1 country: China