A Cell-free tsRNA Signature for Early Detection of Hepatocellular Carcinoma (CENTINEL)

December 3, 2025 updated by: City of Hope Medical Center

A Cell-Free tsRNA-Based Liquid Biopsy Signature for Early Detection of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is often diagnosed at an advanced stage, and early detection is critical for improving patient outcomes. Despite this, reliable non-invasive biomarkers for early-stage HCC are limited.

This study seeks to develop a cell-free tsRNA (cf-tsRNA)-based liquid biopsy assay for accurate detection of early-stage HCC.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Liver cancer is a major global health challenge, ranking as the 5th leading cause of cancer-related deaths in the U.S. and 3rd worldwide, with hepatocellular carcinoma (HCC) accounting for ~75% of cases. Incidence has more than tripled since 1980, and death rates have risen by ~2% annually, highlighting the need for improved detection and treatment. Prognosis remains poor: over 50% of HCC cases are diagnosed at stage IV, with a 1-year survival below 30%, whereas early-stage HCC (stages I-II) can achieve up to 74% 5-year survival with curative interventions. Major risk factors include viral hepatitis (HBV, HCV), alcohol abuse, obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD), with non-viral HCC increasing in prevalence, particularly in Western countries. Screening programs target high-risk populations but miss many asymptomatic or average-risk individuals, contributing to late-stage diagnoses.

Biomarker discovery holds promise for improving early detection. Alpha-fetoprotein (AFP), the most widely used biomarker, has limited sensitivity for early-stage HCC (39-64%). tsRNAs (tRNA-derived small RNAs) are small, single-stranded RNA molecules derived from mature or precursor tRNAs that were first detected in the urine of patients with cancer in the 1970s. Emerging noninvasive markers offer complementary advantages: cell-free tsRNAs (cf-tsRNAs) are stable and highly sensitive for detection. Integrating these biomarker types could enable robust models for accurate early HCC detection, addressing a critical gap in clinical care.

This study seeks to validate a panel of more accurate and non-invasive biomarkers (cf-tsRNAs) in preoperative blood samples. Accurate early detection of HCC would help provide clear criteria for treatment decisions, such as timely surgical intervention or the addition of adjuvant chemotherapy.

Study Type

Observational

Enrollment (Estimated)

600

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Goel Ajay, PhD
  • Phone Number: 626-218-3452
  • Email: ajgoel@coh.org

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91016
        • Recruiting
        • City of Hope Medical Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Individuals who were diagnosed with hepatocellular carcinoma

Description

Inclusion Criteria:

  • A histologically confirmed diagnosis of hepatocellular carcinoma.
  • Received standard diagnostic and staging procedures as per local guidelines
  • Availability of at least one blood-derived sample, drawn before receiving any curative-intent treatment

Exclusion Criteria:

• Lack of or inability to provide informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
HCC (Discovery, Small RNA-seq)
Serum and plasma samples from patients with histologically confirmed HCC will be analyzed using small RNA sequencing to identify circulating tsRNAs specifically upregulated in HCC. These tsRNAs will serve as candidates for downstream validation.
Diagnostic test: Small RNA sequence
Comprehensive small RNA sequencing of serum or plasma-derived cf-tsRNAs to identify candidate biomarkers distinguishing HCC from NDC.
Non-disease Control (Discovery, Small RNA-seq)
Serum and plasma samples from individuals without malignant will be analyzed in parallel by small RNA sequencing to identify tsRNAs differentially expressed between HCC and non-disease controls.
Diagnostic test: Small RNA sequence
Comprehensive small RNA sequencing of serum or plasma-derived cf-tsRNAs to identify candidate biomarkers distinguishing HCC from NDC.
HCC (Training, rt-qPCR)
Serum and plasma samples from patients with histologically confirmed HCC will be analyzed using rt-qPCR to test circulating tsRNAs specifically upregulated in HCC.
Diagnostic test: Rt-qPCR
Construction of integrated cf- tsmiRNAs diagnostic classifier using machine learning
Diagnostic test: Rt-qPCR
PCR-based validation of the tsRNA panel
NDC (Training, rt-qPCR)
Individuals without malignant whose serum/plasma samples will serve as controls to establish baseline tsRNA expression and diagnostic thresholds.
Diagnostic test: Rt-qPCR
Construction of integrated cf- tsmiRNAs diagnostic classifier using machine learning
Diagnostic test: Rt-qPCR
PCR-based validation of the tsRNA panel
HCC (Testing, rt-qPCR)
Independent HCC cohort used for external validation of the panel to confirm diagnostic performance and reproducibility.
Diagnostic test: Rt-qPCR
Construction of integrated cf- tsmiRNAs diagnostic classifier using machine learning
Diagnostic test: Rt-qPCR
PCR-based validation of the tsRNA panel
NDC (Testing, rt-qPCR)
Individuals without malignant whose serum/plasma samples will be used for validation of specificity and model robustness.
Diagnostic test: Rt-qPCR
Construction of integrated cf- tsmiRNAs diagnostic classifier using machine learning
Diagnostic test: Rt-qPCR
PCR-based validation of the tsRNA panel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sensitivity
Time Frame: Through study completion, an average of 1 year
True Positive Rate: the probability of a positive test result, conditioned on the individual truly being positive
Through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Specificity
Time Frame: Through study completion, an average of 1 year
True Negative Rate: the probability of a negative test result, conditioned on the individual truly being negative
Through study completion, an average of 1 year
Proportion of correct predictions (true positives and true negatives) among the total number of cases (i.e.,accuracy)
Time Frame: Through study completion, an average of 1 year
A measure of trueness: proportion of correct predictions (both true positives and true negatives) among the total number of cases examined
Through study completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

City of Hope Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 15, 2025

Primary Completion (Estimated)

June 18, 2026

Study Completion (Estimated)

June 18, 2026

Study Registration Dates

First Submitted

November 24, 2025

First Submitted That Met QC Criteria

November 24, 2025

First Posted (Estimated)

December 4, 2025

Study Record Updates

Last Update Posted (Actual)

December 10, 2025

Last Update Submitted That Met QC Criteria

December 3, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 23228/CENTINEL

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Data collected for the study will be made available to others, including de-identified participant data, at publication, via a signed data access agreement and at the discretion of the investigators' approval of the proposed use of such data.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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