{
  "abstract": "ObjectiveDiabetic foot ulcers (DFUs) affect up to 34% of people with diabetes and precede 80% of lower extremity amputations, yet no ulcer-level molecular biomarkers distinguish healing trajectories. We aimed to identify wound swab proteins associated with DFU healing time and characterize their prognostic potential.\n\nResearch Design and MethodsLC-MS/MS proteomics was performed on wound swabs from 112 people with diabetes presenting with new DFUs, followed for up to 6 months. Participants were divided into fast-healers ([≤]40), slow-healers (41-180 days) and chronic wounds (>180 days). Proteins associated with \"time to healing\" were identified using Firth-penalized Cox regression (FDR<0.2; HR<1 indicated slow healing) and used to construct a cross-validated Protein Healing Score (PHS). Sensitivity and causal mediation analyses examined clinical variable effects on protein abundance, with independent dataset validation.\n\nResultsParticipants had a mean ({+/-}SD) age of 67.5 ({+/-}12.3) years, and diabetes duration of 27.5 ({+/-}14.9) years. Twenty-seven proteins formed two clusters: a slow-healing cluster enriched in neutrophil granule and innate immune proteins (HR<1), and a fast-healing cluster enriched in proteostatic stress proteins (HR>1). Triglyceride levels differed between healing groups (p=0.001); seven slow-healing proteins showed triglyceride-mediated effects (21-28%), suggesting a dyslipidaemia-innate immunity axis. The PHS significantly stratified prognosis (adjusted HR=1.47, 95%CI 1.14-1.89; p=0.003), outperforming clinical variables alone (AUC-OVR 0.71 vs. 0.62). Transcriptomic validation confirmed directional concordance.\n\nConclusionsWound swab proteomics at DFU onset identified a 27-protein healing signature linked to neutrophil-innate immunity and triglyceride associated dyslipidaemia, offering a potential non-invasive prognostic tool.\n\nHighlightsO_LIWhy did we undertake this study? No prior study has examined wound swab protein associations with DFU healing time as a continuous outcome, offering finer prognostic resolution than discrete healing categories. C_LIO_LIWhat is the specific question(s) we wanted to answer? Can wound swab proteins at DFU presentation predict healing trajectories, and do clinical factors mediate these associations? C_LIO_LIWhat did we find? Twenty-seven proteins formed two prognostic clusters: a slow-healing cluster enriched in neutrophil/innate immune proteins and a fast-healing cluster linked to proteostatic stress. A Protein Healing Score outperformed clinical variables in stratifying healing outcomes (AUC-OVR 0.71 vs. 0.62). Triglyceride-mediated and neuropathy-driven effects on wound proteins revealed mechanistic links to impaired healing. C_LIO_LIWhat are the implications of our findings? Wound swab proteomics offers a non-invasive prognostic tool at DFU onset, potentially enabling earlier targeted intervention. C_LI",
  "abstract_shown": true,
  "affiliations": [
    "Steno Diabetes Center Copenhagen, Herlev, Denmark"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "M. Clos-Garcia"
    },
    {
      "name": "S. Y. Jain"
    },
    {
      "name": "C. H. Naaman"
    },
    {
      "name": "J. A. Raguz"
    },
    {
      "name": "Z. Schaefer"
    },
    {
      "name": "G. Kaur"
    },
    {
      "name": "V. R. Curovic"
    },
    {
      "name": "K. Kirketerp-Moller"
    },
    {
      "name": "J. A. Andersen"
    },
    {
      "name": "S. Engberg"
    },
    {
      "name": "A. Rasmussen"
    },
    {
      "name": "A. Veves"
    },
    {
      "name": "P. Rossing"
    },
    {
      "affs": [
        0
      ],
      "name": "T. S. Ahluwalia"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e4ky5bwdx2mz6.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.15.26363101",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.15.26363101v1.full",
  "id": "e4ky5bwdx2mz6",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.15.26363101v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "endocrinology"
    ],
    [
      "openalex",
      "2712|Diabetic Foot Ulcer Assessment and Management"
    ]
  ],
  "openalex": "W7213423571",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.15.26363101v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-15",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/e4ky5bwdx2mz6.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:42Z",
      "native_id": "10.64898/2026.09.15.26363101",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.15.26363101v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:endocrinology",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "Noninvasive Wound Swab Proteomics Enables Prognostic Stratification of Diabetic Foot Ulcer Healing: The HEAL-DFU Proof-of-Concept Study",
  "title_text": "Noninvasive Wound Swab Proteomics Enables Prognostic Stratification of Diabetic Foot Ulcer Healing: The HEAL-DFU Proof-of-Concept Study",
  "type": "preprint",
  "updated_at": "2026-10-30T12:18:42Z",
  "url": "https://research.draconitic.com/paper/e4ky5bwdx2mz6",
  "venue": "medRxiv",
  "versions": []
}