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Metabolomic liquid biopsy dynamics predict early-stage HCC and actionable candidates of human hepatocarcinogenesis.

Kornelius Schulze1,2, Tim Daniel Rose3,4, Lorenz Adlung1,5,6

  • 1I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

JHEP Reports : Innovation in Hepatology
|April 28, 2025
PubMed
Summary
This summary is machine-generated.

Serum metabolome profiling accurately detects early-stage hepatocellular carcinoma (HCC) using a blood-based metabolite signature. This approach identifies actionable targets for chemoprevention and improves upon current surveillance methods.

Keywords:
Early detectionLiver cancerMetabolismPreventionSurveillanceTumorigenesis

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Area of Science:

  • Oncology
  • Metabolomics
  • Biomarker Discovery

Background:

  • Hepatocellular carcinoma (HCC) detection tools are suboptimal, and actionable therapeutic targets remain elusive.
  • Deregulated cellular metabolism is a hallmark of cancer, with circulating metabolites linked to HCC, particularly in fatty liver disease.
  • Current strategies for HCC primary prevention or early detection are lacking.

Purpose of the Study:

  • To demonstrate that serum metabolome profiles reflect hepatocarcinogenesis initiation.
  • To identify biomarkers for early HCC detection.
  • To identify actionable candidates for chemoprevention.

Main Methods:

  • Global cohort study with 654 patients and 801 biospecimens, including serum metabolome profiling.
  • Phase II biomarker case-control study for early HCC detection.
  • Validation through in silico analysis, mRNA sequencing, proteome profiling, and in vitro experiments.

Main Results:

  • Serum levels of aspartic acid, glutamic acid, taurine, and hypoxanthine were altered across liver disease stages.
  • A blood-based metabolite signature achieved 94% AUC for early HCC detection versus cirrhosis.
  • Identified actionable targets (RRM2, GMPS, BCAT1, PYCR2, NEU1) in tumor tissue with validated roles in proliferation and migration.

Conclusions:

  • Serum metabolome profiling reveals deregulated metabolites and pathways in hepatocarcinogenesis.
  • A liquid biopsy approach accurately detects early-stage HCC, outperforming current surveillance.
  • Identified actionable targets for chemoprevention and provides rationale for clinical trials.