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Recruiting NCT07265271

Project for Multi-Omics-Based Early Detection of Hepatocellular Carcinoma (PROMETHEA Study)

— Observational Hepatocellular Carcinoma (HCC)

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Small RNA sequence, Rt-qPCR, Rt-qPCR.
Who it may be relevant to
Registry conditions: Hepatocellular Carcinoma (HCC). Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Overview

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 multi-omics-based liquid biopsy assay, especially focusing on ncRNAs (e.g. tsRNA, miRNA, circRNA, lncRNA, etc.) for accurate detection of early-stage HCC.

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%).

This study seeks to validate a panel of more accurate and non-invasive biomarkers 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.

Interventions

  • Diagnostic test Small RNA sequence
    Comprehensive small RNA sequencing of serum or plasma-derived cf-tsRNAs to identify candidate biomarkers distinguishing HCC from NDC.
  • 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

Primary outcome measures

  • Diagnostic performance of the integrated multi-omics signature for hepatocellular carcinoma detection [Time frame: At the baseline]
Secondary outcome measures (2)
  • Validation of the diagnostic model in independent cohorts [Time frame: At the baseline]
  • Identification of etiology-associated omics profiles in hepatocellular carcinoma [Time frame: At the baseline]

Eligibility criteria

Inclusion criteria

  • Adults aged 18 to 100 years.
  • A histologically confirmed diagnosis of hepatocellular carcinoma.
  • A clinically diagnosed as chronic liver disease, including chronic hepatitis or liver cirrhosis, without evidence of hepatocellular carcinoma.
  • Healthy volunteers without known liver disease or malignancy.
  • Received standard diagnostic and staging procedures as per local guidelines
  • Availability of blood or other biospecimens.
  • Ability to provide written informed consent.

Exclusion criteria

  • Lack of or inability to provide informed consent
  • History of other active malignancies within the past 5 years
  • Previous liver transplantation
  • Severe systemic infection or inflammatory disease at the time of enrollment
  • Inadequate sample quality or quantity

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model
Case-control

Study locations

United States · 1 center
  • City of Hope Medical Center — Duarte

Publications

  • Shao Y, Yu X, Zhou W, Yan J, Dong H, Ye G. Biological roles and potential clinical value of tRNA-derived small RNAs in gastrointestinal malignancies. Ann Med. 2025 Dec;57(1):2566866. doi: 10.1080/07853890.2025.2566866. Epub 2025 Oct 9. PMID 41069160
  • Mao M, Chen W, Huang X, Ye D. Role of tRNA-derived small RNAs(tsRNAs) in the diagnosis and treatment of malignant tumours. Cell Commun Signal. 2023 Jul 21;21(1):178. doi: 10.1186/s12964-023-01199-w. PMID 37480078
  • Lee S, Kim J, Valdmanis PN, Kim HK. Emerging roles of tRNA-derived small RNAs in cancer biology. Exp Mol Med. 2023 Jul;55(7):1293-1304. doi: 10.1038/s12276-023-01038-5. Epub 2023 Jul 10. PMID 37430089
  • Zhou M, He X, Zhang J, Mei C, Zhong B, Ou C. tRNA-derived small RNAs in human cancers: roles, mechanisms, and clinical application. Mol Cancer. 2024 Apr 15;23(1):76. doi: 10.1186/s12943-024-01992-2. PMID 38622694
  • Yuan J, Gu WC, Xu TX, Shen XJ, Li X, Shen L, Zhang Y, Ju SQ. 5'-transfer RNA halve-lysine-CTT as a promising biomarker for early detection of hepatocellular carcinoma. World J Gastrointest Oncol. 2025 Nov 15;17(11):111142. doi: 10.4251/wjgo.v17.i11.111142. PMID 41281472
  • Sauzay C, Petit A, Bourgeois AM, Barbare JC, Chauffert B, Galmiche A, Houessinon A. Alpha-foetoprotein (AFP): A multi-purpose marker in hepatocellular carcinoma. Clin Chim Acta. 2016 Dec 1;463:39-44. doi: 10.1016/j.cca.2016.10.006. Epub 2016 Oct 11. PMID 27732875
  • Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S, Lencioni R, Koike K, Zucman-Rossi J, Finn RS. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021 Jan 21;7(1):6. doi: 10.1038/s41572-020-00240-3. PMID 33479224
  • Xing H, Zheng YJ, Han J, Zhang H, Li ZL, Lau WY, Shen F, Yang T. Protein induced by vitamin K absence or antagonist-II versus alpha-fetoprotein in the diagnosis of hepatocellular carcinoma: A systematic review with meta-analysis. Hepatobiliary Pancreat Dis Int. 2018 Dec;17(6):487-495. doi: 10.1016/j.hbpd.2018.09.009. Epub 2018 Sep 15. PMID 30257796

Identifiers

NCT: NCT07265271 · 23228/CENTINEL

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗