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  11. Aberrant Fragmentomic Features Of Circulating Cell-free Mitochondrial Dna Enable Early Detection And Prognosis Prediction Of Hepatocellular Carcinoma

Aberrant fragmentomic features of circulating cell-free mitochondrial DNA enable early detection and prognosis prediction of hepatocellular carcinoma

Yang Liu1,2, Fan Peng1, Siyuan Wang1

  • 1State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and Department of Physiology and Pathophysiology, Fourth Military Medical University, Xi'an, China.

Clinical and Molecular Hepatology
|October 15, 2024

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View abstract on PubMed

Summary
This summary is machine-generated.

This study introduces a novel, low-cost method using circulating cell-free mitochondrial DNA (ccf-mtDNA) fragmentomics for early hepatocellular carcinoma (HCC) detection and prognosis. The developed models demonstrate high accuracy, outperforming current standards for improved patient survival.

Area of Science:

  • Oncology
  • Genomics
  • Biomarker Discovery

Background:

  • Hepatocellular carcinoma (HCC) detection and prognosis require improved, cost-effective methods.
  • Circulating cell-free mitochondrial DNA (ccf-mtDNA) fragmentomics presents a potential avenue for non-invasive diagnostics.

Purpose of the Study:

  • To develop ultra-sensitive, low-cost HCC detection and prognosis models using ccf-mtDNA fragmentomic features.
  • To validate the clinical utility of these models in a large cohort.

Main Methods:

  • Capture-based mtDNA sequencing was performed on plasma cfDNA from 1168 participants (571 HCC, 301 CHB/LC, 296 HC).
  • A random forest algorithm was used for HCC detection model construction.
  • LASSO-Cox regression was employed for HCC prognosis prediction model development.
Keywords:
Circulating cell free mitochondrial DNAEarly diagnosisFragmentomicsHepatocellular carcinoma

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Main Results:

  • Aberrant ccf-mtDNA fragmentomic features were significantly identified in HCC patients.
  • The HCC detection model achieved AUC > 0.983, sensitivity > 89.6%, and specificity > 95.00% in validation cohorts, surpassing AFP and mtDNA copy number.
  • The prognosis model accurately predicted 1- to 3-year survival (AUCs ranging from 0.7958 to 0.8333).

Conclusions:

  • A high-performing, low-cost approach utilizing ccf-mtDNA fragmentomics for HCC early detection and prognosis has been developed and validated.
  • This method shows promising clinical translational applications for improving HCC patient outcomes.
prognosis