{
  "abstract": "Circulating cell-free epigenetic and epitranscriptomic modifications (epimarks) are emerging as minimally invasive biomarkers for cancer detection and therapeutic monitoring. Their clinical utility in non-small cell lung cancer (NSCLC), particularly in the context of EGFR-targeted therapies, remains to be fully established. Ten circulating epimarks encompassing cfRNA methylation, histone post-translational modifications on circulating nucleosomes, and cfDNA methylation were quantified in plasma samples from healthy donors and metastatic NSCLC patients with mutant or wild-type EGFR. Longitudinal analyses were performed in EGFR-mutant patients treated with tyrosine kinase inhibitors (TKIs). Functional relevance was assessed using in vitro and in ovo models of Osimertinib-sensitive and -resistant NSCLC cells combined with targeted epigenetic inhibitors. Distinct epimark signatures accurately discriminated healthy donors from NSCLC patients and distinguished EGFR-mutant from EGFR–wild-type tumors. cfRNA methylation marks (m1A, m6A, m5C, and m7G) showed excellent diagnostic performance, with a composite methyl-cfRNA score robustly distinguishing EGFR-mutant NSCLC. Disease progression under TKI therapy was characterized by increased m1A-cfRNA, H3K23Ac- and H4R3me2-circulating nucleosomes and decreased 5mC-cfDNA, with m1A-cfRNA alone reliably tracking progression. High m6A-cfRNA levels at diagnosis were strongly associated with shorter progression-free survival. Functionally, Osimertinib resistance promoted tumor growth and metastatic dissemination. Combination therapies targeting METTL3, KAT6A, or PRMT5 with Osimertinib reduced tumor burden and metastasis through miRNA-dependent regulation of histone acetylation and methylation. Circulating epimarks represent promosing diagnostic and prognostic biomarkers and provide a mechanistic basis for epigenetic combination therapies in EGFR-driven NSCLC.",
  "abstract_shown": true,
  "affiliations": [
    "Inserm UMR 1307, CNRS UMR 6075, Nantes Université, Université d’Angers, CRCI2NA",
    "CRCI2NA, INSERM 1307, CNRS 6075, Institut de Cancérologie de L’Ouest",
    "Centre Hopitalier Universitaire de Toulouse",
    "Intergroupe Francophone de Cancérologie Thoracique (IFCT)",
    "Service des Maladies Respiratoires, Centre Hospitalier Le Mans"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Dorian Espi-Bastien"
    },
    {
      "affs": [
        0
      ],
      "name": "Judith Raimbourg"
    },
    {
      "affs": [
        0
      ],
      "name": "Gwenola Bougras-Cartron"
    },
    {
      "affs": [
        0
      ],
      "name": "Arulraj Nadaradjane"
    },
    {
      "affs": [
        0
      ],
      "name": "Séverine Blondeau"
    },
    {
      "affs": [
        0
      ],
      "name": "Guillaume Dupas"
    },
    {
      "affs": [
        1
      ],
      "name": "Bertrand Volard"
    },
    {
      "affs": [
        0
      ],
      "name": "Armelle Lefrançois"
    },
    {
      "affs": [
        0
      ],
      "name": "Fabien Gautier"
    },
    {
      "affs": [
        2
      ],
      "name": "Julien Mazières"
    },
    {
      "affs": [
        3
      ],
      "name": "Franck Morin"
    },
    {
      "affs": [
        3
      ],
      "name": "Olivier Molinier"
    },
    {
      "affs": [
        4
      ],
      "name": "Fabrice Barlesi"
    },
    {
      "affs": [
        3
      ],
      "name": "Elodie Amour"
    },
    {
      "affs": [
        0
      ],
      "name": "Mathilde Dupé"
    },
    {
      "affs": [
        0
      ],
      "name": "Pierre-François Cartron"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a9fbhswj2qd2y.bib",
  "cited_by": 1,
  "doi": "10.1038/s41598-026-62035-y",
  "fulltext_url": "https://doi.org/10.1038/s41598-026-62035-y",
  "id": "a9fbhswj2qd2y",
  "issns": [
    "2045-2322"
  ],
  "landing_url": "https://doi.org/10.1038/s41598-026-62035-y",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "Q"
    ],
    [
      "lcc",
      "R"
    ],
    [
      "openalex",
      "1306|Cancer Genomics and Diagnostics"
    ]
  ],
  "openalex": "W7169757662",
  "pdf_url": "https://www.nature.com/articles/s41598-026-62035-y_reference.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-01",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/a9fbhswj2qd2y.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:45:50Z",
      "native_id": "ec6957491bc04f61bff5c3496e336438",
      "source": "doaj",
      "url": "https://doi.org/10.1038/s41598-026-62035-y"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Cancer Genomics and Diagnostics",
      "subfield": "oncology"
    }
  ],
  "title": "Circulating epigenetic and epitranscriptomic biomarkers identify EGFR status, predict TKI response and reveal therapeutic vulnerabilities in NSCLC",
  "title_text": "Circulating epigenetic and epitranscriptomic biomarkers identify EGFR status, predict TKI response and reveal therapeutic vulnerabilities in NSCLC",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:45:50Z",
  "url": "https://research.draconitic.com/paper/a9fbhswj2qd2y",
  "venue": "Scientific Reports",
  "versions": []
}