{
  "abstract": "Esophageal cancer (EC) is highly lethal due to late diagnosis, and accurate non-invasive tools for early detection and subtyping remain lacking. Circulating cell-free mitochondrial DNA (ccf-mtDNA) fragmentomics offers a promising biomarker source. In this large multi-center study enrolling 1,260 participants spanning healthy control (HC), benign esophageal diseases (BED), precancerous lesions and EC patients, we developed two machine learning models based on plasma ccf-mtDNA fragmentomic profiles: an EC detection (ED) model and a pathological subtyping prediction (PSP) model. The ED model achieved an AUC of 0.9706 (EC vs. non-EC) in the training cohort, with high performance in internal (0.9762), external (0.9748), and Chinese minority (0.9668, Uyghur and Kazakh) validation cohorts. At the optimal cut-off, it yielded 92.16% sensitivity for stage I EC in the combined validation cohort and correctly identified 93.10% of early EC cases missed by preoperative biopsy. It also discriminated high-grade intraepithelial neoplasia from non-EC with an AUC of 0.9597. The PSP model distinguished ESCC from EAC with 89.71% accuracy, improving to 90.74% after integrating key clinical parameters. In summary, ccf-mtDNA fragmentomics provides a robust, non-invasive platform for early EC detection, precancerous risk stratification, and histological subtyping, demonstrating strong potential to transform clinical management.",
  "abstract_shown": true,
  "affiliations": [
    "State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and Department of Physiology and Pathophysiology, Fourth Military Medical University, Xi'an, China.",
    "College of Medical Technology, Shaanxi University of Chinese Medicine, Xianyang, China.",
    "Department of Clinical Laboratory, The First Affiliated Hospital of Air Force Medical University, Xi'an, China.",
    "Clinical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, China.",
    "Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.",
    "State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and Department of Clinical Diagnosis, Tangdu Hospital, Fourth Military Medical University, Xi'an, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yue Liu",
      "orcid": "0009-0005-2831-5199"
    },
    {
      "affs": [
        1
      ],
      "name": "Wenying Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yu Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Siyuan Wang"
    },
    {
      "affs": [
        2
      ],
      "name": "Xiang Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Fan Peng"
    },
    {
      "affs": [
        0
      ],
      "name": "Miao Dang",
      "orcid": "0009-0003-4467-4269"
    },
    {
      "affs": [
        0
      ],
      "name": "Huanqin Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Huanmin Jiao"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuqing Yang"
    },
    {
      "affs": [
        3
      ],
      "name": "Zhaoquan Su",
      "orcid": "0009-0009-3847-1178"
    },
    {
      "affs": [
        3
      ],
      "name": "Xiumin Ma",
      "orcid": "0000-0001-8011-7513"
    },
    {
      "affs": [
        4
      ],
      "name": "Zhiyun Gong"
    },
    {
      "affs": [
        4
      ],
      "name": "Renquan Lu",
      "orcid": "0000-0003-3291-5742"
    },
    {
      "affs": [
        0
      ],
      "name": "Jinliang Xing",
      "orcid": "0000-0003-2532-7029"
    },
    {
      "affs": [
        5
      ],
      "name": "Yang Liu",
      "orcid": "0009-0007-3811-6163"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/apnjq3zwkkgwz.bib",
  "cited_by": 0,
  "doi": "10.1002/advs.78377",
  "fulltext_url": "https://europepmc.org/articles/PMC13715668",
  "id": "apnjq3zwkkgwz",
  "issns": [
    "2198-3844"
  ],
  "landing_url": "https://europepmc.org/article/MED/42949655",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2746|Esophageal Cancer Research and Treatment"
    ]
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  "openalex": "W7224132820",
  "pdf_url": "https://europepmc.org/articles/PMC13715668?pdf=render",
  "pmcid": "PMC13715668",
  "pmid": "42949655",
  "published": "2026-10-28",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/apnjq3zwkkgwz.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:33Z",
      "native_id": "MED:42949655",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42949655"
    },
    {
      "first_seen": "2026-11-01T12:22:54Z",
      "native_id": "PMC13715668",
      "source": "pmc",
      "url": "https://doi.org/10.1002/advs.78377"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2746|Esophageal Cancer Research and Treatment",
      "subfield": "surgery"
    }
  ],
  "title": "Noninvasive Detection and Subtyping of Esophageal Cancer by Circulating Cell-Free mtDNA Fragmentomics: A Multi-Center Validation Study.",
  "title_text": "Noninvasive Detection and Subtyping of Esophageal Cancer by Circulating Cell-Free mtDNA Fragmentomics: A Multi-Center Validation Study.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:22:54Z",
  "url": "https://research.draconitic.com/paper/apnjq3zwkkgwz",
  "venue": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)",
  "versions": []
}