{
  "abstract": "Background: Cancer-related sarcopenia is associated with poor clinical outcomes but remains difficult to define and quantify in routine oncology practice. Current assessments rely on imaging and functional scales that are time-consuming and provide limited biological insight. We aimed to identify a plasma proteomic signature of cancer-related sarcopenia and to uncover circulating mediators involved in its pathophysiology. Methods: Patients were included from two cohorts of the MATCH-R study (NCT02517892): a discovery cohort of advanced cancer patients treated with immunotherapy and an independent validation cohort of metastatic castration-resistant prostate cancer (mCRPC) patients treated with androgen-receptor pathway inhibitors. External validation was performed in the TRACERx cohort of non-small cell lung cancer. Skeletal muscle index at third lumbar vertebra (L3) was quantified using imaging, and ECOG performance status served as a functional proxy. Plasma proteomics was performed using the Olink Explore platform. An extreme gradient boosting (XGBoost) model was trained on a high-contrast subset using a neuromuscular-focused protein panel and validated across cohorts. Functional effects of candidate mediators were assessed in differentiating human myoblasts. Results: The model generated a continuous sarcopenia probability (SP) score that correlated with muscle mass and functional status and consistently stratified overall survival across cohorts. A reduced four-protein model retained comparable performance, supporting translational applicability. Proteins associated with SP included insulin-like growth factor binding protein 1 and 2 (IGFBP1, IGFBP2), and interleukin-6 (IL6). IGFBP1 and IGFBP2 impaired myoblast differentiation, while IL6 induced IGFBP1 expression in liver cells. Conclusions: Plasma proteomics enables scalable and biologically informed assessment of cancer-related sarcopenia, identifies tumor-host mediators of muscle dysfunction, and supports objective patient stratification for therapeutic intervention.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 27,
  "authors": [
    {
      "name": "Filippo Gustavo Dall’olio"
    },
    {
      "name": "Wael Salem Zrafi"
    },
    {
      "name": "Xinran Song"
    },
    {
      "name": "Littisha Lawrance"
    },
    {
      "name": "Ekaterina Shalimanova"
    },
    {
      "name": "Anna Schwager"
    },
    {
      "name": "Nadia Myszka"
    },
    {
      "name": "Fei Chen"
    },
    {
      "name": "Rebecca Ibrahim"
    },
    {
      "name": "Marie Guinhut"
    },
    {
      "name": "Pierre Busson"
    },
    {
      "name": "Catherine Brenner"
    },
    {
      "name": "Karim Benihoud"
    },
    {
      "name": "Fabrice Barlesi"
    },
    {
      "name": "Caroline Even"
    },
    {
      "name": "Dimitria Brempou"
    },
    {
      "name": "Nathalie Lassau"
    },
    {
      "name": "Claudio Nicotra"
    },
    {
      "name": "Maud Ngo Camus"
    },
    {
      "name": "Marine Aglave"
    },
    {
      "name": "Yohann Loriot"
    },
    {
      "name": "Diana Cardenas"
    },
    {
      "name": "Mariam Jamal-Hanjani"
    },
    {
      "name": "Carla M Prado"
    },
    {
      "name": "Antoine Italiano"
    },
    {
      "name": "Yegor Vassetzky"
    },
    {
      "name": "Benjamin Besse"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7c9y320bj6105.bib",
  "cited_by": 0,
  "doi": "10.1186/s12943-026-02716-4",
  "fulltext_url": null,
  "id": "7c9y320bj6105",
  "issns": [
    "1476-4598"
  ],
  "landing_url": "https://hal.science/hal-05760261v1",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "2737|Nutrition and Health in Aging"
    ]
  ],
  "openalex": "W7166563782",
  "pdf_url": "https://hal.science/hal-05760261/document",
  "pmcid": null,
  "pmid": "42374406",
  "published": "2026-06-29",
  "publisher": "BioMed Central",
  "ris": "https://research.draconitic.com/paper/7c9y320bj6105.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:39Z",
      "native_id": "hal-05760261",
      "source": "hal",
      "url": "https://hal.science/hal-05760261v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Nutrition and Health in Aging",
      "subfield": "physiology"
    }
  ],
  "title": "A plasma proteomic signature of cancer-related sarcopenia implicates the IGFBP axis in muscle dysfunction",
  "title_text": "A plasma proteomic signature of cancer-related sarcopenia implicates the IGFBP axis in muscle dysfunction",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:39Z",
  "url": "https://research.draconitic.com/paper/7c9y320bj6105",
  "venue": "Molecular Cancer",
  "versions": []
}