ArticleCancers2025
Somatic Copy Number Alterations in Circulating Cell-Free DNA as a Prognostic Biomarker for Hepatocellular Carcinoma: Insights from a Proof-of-Concept Study.
Article in Cancers, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Genomics and Epigenomics Approaches for the Quantification of Circulating Tumor DNA in Liquid Biopsy: Relevance of a Multimodal Strategy.International journal of molecular sciences · 2025Review
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16 authors.
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Abstract
BACKGROUND/
objectivesDespite advances in hepatocellular carcinoma (HCC) management, prognosis remains poor. Advanced-stage diagnosis often excludes curative treatments, and current biomarkers (e.g., alpha-fetoprotein [AFP]) have limited utility in early detection. Liquid biopsy has emerged as a promising cancer detection tool, with circulating cell-free DNA (ccfDNA) showing significant diagnostic potential. This proof-of-concept study aimed to investigate the potential role of tumor fraction (TF) within ccfDNA as a biomarker in HCC patients.
methodsA total of sixty patients were recruited, including thirteen with chronic liver disease (CLD), twenty-four with cirrhosis, and twenty-three with HCC. Plasma samples were collected, and ccfDNA was extracted for shallow whole genome sequencing (sWGS) analysis. The TF was calculated by focusing on somatic copy number alterations (SCNAs) within the ccfDNA.
resultsAmong patients with CLD and cirrhosis (n = 37), ctDNA was undetectable in all but one cirrhotic patient who exhibited a significant tumor fraction (TF) of 17% and subsequently developed HCC. Conversely, five out of twenty-three HCC patients (21.7%) displayed detectable ctDNA with TF levels ranging from 3.0% to 32.6%. Patients with detectable ctDNA were characterized by more aggressive oncological features, including a higher number of nodules (
conclusionsOur results suggest that the analysis of TF by sWGS is a promising non-invasive tool for the identification of HCC with aggressive clinical behavior, whereas it is not sensitive enough for early HCC detection. This molecular assay can improve prognostic stratification in HCC patients.
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