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

NCT07265271 | Recruiting

• 1 other identifier: 23228/CENTINEL
• Study Type: observational
• Target: 600
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hepatocellular Carcinoma (HCC)

Keywords

HCC; Liver cancer; tsRNA; Liquid Biopsy; Early Detection

Outcome Measures

Primary Outcomes (1)

• Sensitivity

  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 Outcomes (2)

• Specificity

  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)

  Through study completion, an average of 1 year

Study Arms (6)

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

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

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

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

HCC (Testing, rt-qPCR)

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

Diagnostic Test: Rt-qPCR

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

Interventions

Small RNA sequence DIAGNOSTIC_TEST

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

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

Rt-qPCR DIAGNOSTIC_TEST

Construction of integrated cf- tsmiRNAs diagnostic classifier using machine learning

HCC (Training, rt-qPCR); NDC (Training, rt-qPCR)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals who were diagnosed with hepatocellular carcinoma

You may qualify if:

• 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

You may not qualify if:

• Lack of or inability to provide informed consent

Sponsors & Collaborators

• City of Hope Medical Center: lead

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91016, United States

RECRUITING

Related Publications (11)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Choi JY, Jung SW, Kim HY, Kim M, Kim Y, Kim DG, Oh EJ. Diagnostic value of AFP-L3 and PIVKA-II in hepatocellular carcinoma according to total-AFP. World J Gastroenterol. 2013 Jan 21;19(3):339-46. doi: 10.3748/wjg.v19.i3.339.

  PMID: 23372355 BACKGROUND

• Xu J, Chen B, Qi J, Wu J, Feng W, Jin K, Bao H, Chen L, Wang F. Evaluation of serum hsa_tsr014055 as a potential biomarker for diagnosis and prognosis of hepatocellular carcinoma. Ann Med. 2025 Dec;57(1):2528978. doi: 10.1080/07853890.2025.2528978. Epub 2025 Jul 6.

  PMID: 40618217 BACKGROUND

• Jin K, Wu J, Yang J, Chen B, Xu J, Bao H, Zong W, Xie C, Chen L, Wang F. Identification of serum tsRNA-Thr-5-0015 and combined with AFP and PIVKA-II as novel biomarkers for hepatocellular carcinoma. Sci Rep. 2024 Nov 21;14(1):28834. doi: 10.1038/s41598-024-80592-y.

  PMID: 39572775 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma or serum

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Central Study Contacts

Goel Ajay, PhD

CONTACT

626-218-3452; ajgoel@coh.org

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2025
• First Posted: December 4, 2025
• Study Start: January 15, 2025
• Primary Completion (Estimated): June 18, 2026
• Study Completion (Estimated): June 18, 2026
• Last Updated: December 10, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)