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

Обзор

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.

Подробное описание

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.

Вмешательства

• Диагностический тест Small RNA sequence
  Comprehensive small RNA sequencing of serum or plasma-derived cf-tsRNAs to identify candidate biomarkers distinguishing HCC from NDC.
• Диагностический тест Rt-qPCR
  Construction of integrated cf- tsmiRNAs diagnostic classifier using machine learning
• Диагностический тест Rt-qPCR
  PCR-based validation of the tsRNA panel

Первичные конечные точки

• Diagnostic performance of the integrated multi-omics signature for hepatocellular carcinoma detection [Срок оценки: At the baseline]

Вторичные конечные точки (2)

• Validation of the diagnostic model in independent cohorts [Срок оценки: At the baseline]
• Identification of etiology-associated omics profiles in hepatocellular carcinoma [Срок оценки: At the baseline]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

США · 1 центр

• City of Hope Medical Center — Duarte

Публикации

• 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

Идентификаторы

NCT: NCT07265271 · 23228/CENTINEL

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗