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

City of Hope

Status

Enrolling

Conditions

Hepatocellular Carcinoma (HCC)

Treatments

Diagnostic Test: Rt-qPCR

Diagnostic Test: Small RNA sequence

Study type

Observational

Funder types

Other

Identifiers

NCT07265271

23228/CENTINEL

Details and patient eligibility

About

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.

Full 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.

Enrollment

600 estimated patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

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

Trial design

600 participants in 6 patient groups

HCC (Discovery, Small RNA-seq)

Description:

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.

Treatment:

Diagnostic Test: Small RNA sequence

Non-disease Control (Discovery, Small RNA-seq)

Description:

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.

Treatment:

Diagnostic Test: Small RNA sequence

HCC (Training, rt-qPCR)

Description:

Serum and plasma samples from patients with histologically confirmed HCC will be analyzed using rt-qPCR to test circulating tsRNAs specifically upregulated in HCC.

Treatment:

Diagnostic Test: Rt-qPCR

NDC (Training, rt-qPCR)

Description:

Individuals without malignant whose serum/plasma samples will serve as controls to establish baseline tsRNA expression and diagnostic thresholds.

Treatment:

Diagnostic Test: Rt-qPCR

HCC (Testing, rt-qPCR)

Description:

Independent HCC cohort used for external validation of the panel to confirm diagnostic performance and reproducibility.

Treatment:

Diagnostic Test: Rt-qPCR