{
  "abstract": "Early detection of hepatocellular carcinoma (HCC) remains challenging, as the currently recommended surveillance strategy based on ultrasound combined with alpha-fetoprotein (AFP) is limited by suboptimal sensitivity and accessibility. Cell-free DNA (cfDNA) provides a minimally invasive avenue for cancer detection. However, most existing cfDNA-based approaches either perform unreliably in low-input samples or require analytically complex workflows. Here, we systematically profiled serum cfDNA from individuals with HCC and without HCC and identified a high-abundance tumor-associated single cfDNA fragment at the FAM230F genomic region. Integrative analysis of liver assay for transposase-accessible chromatin with sequencing (ATAC-seq) data revealed consistent tumor-specific chromatin accessibility at this locus, suggesting a tumor-derived origin. Structural characterization further demonstrated enrichment of G-quadruplex (G4) features within the target sequence, which may increase resistance to serum nuclease degradation and promote its preferential retention in circulation. Based on these properties, we established a qPCR-based detection workflow with clinical accessibility. In a validation cohort independent of the discovery cohort, a ΔCt cutoff of 2 was selected by maximizing the Youden index within the same cohort. The assay showed a sensitivity of 94.5% and a specificity of 90.5% for distinguishing HCC from non-HCC. Collectively, our study identifies FAM230F as a structurally stable tumor-associated cfDNA fragment and establishes a simple and scalable qPCR-based assay for HCC detection, providing a practical framework for translating cfDNA fragment analysis into clinical biomarkers.",
  "abstract_shown": true,
  "affiliations": [
    "School of Biomedical Engineering & Suzhou Institute for Advanced Research, University of Science and Technology of China Suzhou 215123 China",
    "New Cornerstone Science Laboratory, Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University Beijing 100084 China",
    "Department of Hepatobiliary Surgery, State Key Laboratory of Immune Response and Immunotherapy, Anhui Provincial Clinical Research Center for Hepatobiliary Diseases, Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of University of Science and Technology of China (USTC), University of Science and Technology of China Hefei China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Jianzhe Sun",
      "orcid": "0009-0005-1162-4032"
    },
    {
      "affs": [
        0
      ],
      "name": "Xucong Teng",
      "orcid": "0000-0002-1514-0562"
    },
    {
      "affs": [
        2
      ],
      "name": "Weizhi Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yicong Dai",
      "orcid": "0000-0001-6503-965X"
    },
    {
      "affs": [
        2
      ],
      "name": "Lianxin Liu",
      "orcid": "0000-0002-3535-6467"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jinghong Li",
      "orcid": "0000-0002-0750-7352"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/64azppkq534jx.bib",
  "cited_by": 0,
  "doi": "10.1039/d6sc04173f",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13564257/",
  "id": "64azppkq534jx",
  "issns": [
    "2041-6520",
    "2041-6539"
  ],
  "landing_url": "https://doi.org/10.1039/d6sc04173f",
  "language": "en",
  "licence": "CC-BY-NC-3.0",
  "licence_label": "CC BY-NC 3.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/3.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Chemistry"
    ],
    [
      "openalex",
      "1306|Cancer Genomics and Diagnostics"
    ]
  ],
  "openalex": "W7207609171",
  "pdf_url": "https://pubs.rsc.org/sc/article-pdf/doi/10.1039/D6SC04173F/13750512/d6sc04173f.pdf",
  "pmcid": "PMC13564257",
  "pmid": "42729963",
  "published": "2026-09-03",
  "publisher": "Royal Society of Chemistry",
  "ris": "https://research.draconitic.com/paper/64azppkq534jx.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:23:46Z",
      "native_id": "PMC13564257",
      "source": "pmc",
      "url": "https://doi.org/10.1039/d6sc04173f"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Cancer Genomics and Diagnostics",
      "subfield": "oncology"
    }
  ],
  "title": "Identification of a G-quadruplex-forming cell-free DNA fragment as a biomarker for the precise diagnosis of hepatocellular carcinoma",
  "title_text": "Identification of a G-quadruplex-forming cell-free DNA fragment as a biomarker for the precise diagnosis of hepatocellular carcinoma",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:20:53Z",
  "url": "https://research.draconitic.com/paper/64azppkq534jx",
  "venue": "Chemical Science",
  "versions": []
}