{
  "abstract": "Background: Adhesive capsulitis (AC) is a fibroinflammatory disorder characterized by painful shoulder restriction and progressive capsular fibrosis. Whether regulated cell-death (RCD) programs are consistently altered across independent transcriptomic cohorts remains uncertain.\n\nMethods: We reanalyzed three public bulk RNA-seq cohorts. GSE140731 was the discovery cohort (22 AC and 26 shoulder-instability surgical controls), and GSE190023 and GSE238053 were independent validation cohorts. Differential expression was estimated from filtered raw counts with PyDESeq2, with age/sex adjustment in GSE140731. Curated pyroptosis, ferroptosis, and necroptosis gene sets; immune marker–gene scores; pathway enrichment; STRING network structure; cross-cohort concordance; an exploratory three-gene classifier; and qPCR validation of four selected genes in TGF-β1-stimulated SW982 cells were evaluated.\n\nResults: The adjusted discovery analysis identified 439 upregulated and 113 downregulated genes at FDR < 0.05. ECM–receptor interaction was strongly positively enriched (NES = 2.299, q = 0.001), making extracellular-matrix remodeling the clearest pathway-level signal. RCD findings were mixed: pyroptosis was not different (delta = −0.105, q = 0.708), ferroptosis was lower but borderline after FDR correction (delta = −0.426, q = 0.056), and necroptosis was lower (delta = −0.320, q = 0.035); the core necroptosis gene set was also negatively enriched (NES = −1.673, q = 0.038). Six immune marker scores were FDR-significant in discovery, but none replicated at cohort-wise FDR significance in the validation cohorts. Cross-cohort gene-effect concordance was heterogeneous (Spearman rho = −0.047 for GSE190023 and 0.383 for GSE238053). The COL11A1–SPON2–PITPNC1 classifier achieved a pooled out-of-fold AUC of 0.820 (95% CI, 0.684–0.930) in GSE140731; external-cohort AUCs ranged from 0.750 to 0.812 with wide confidence intervals, and non-nested feature selection precluded claims of clinical utility. qPCR showed higher COL11A1 and SPON2 and lower PLA2G4A expression after TGF-β1 stimulation, whereas PITPNC1 did not differ significantly, providing model-specific support without establishing causal or clinical validity.\n\nConclusion: Across the three cohorts, ECM remodeling was the most reproducible feature of AC, whereas RCD- and immune-related signals were cohort-dependent and did not support uniform activation of pyroptosis, ferroptosis, or necroptosis. The classifier and RCD signatures remain hypothesis-generating. The SW982 qPCR results provide model-specific experimental support for selected candidates, but broader functional validation in primary AC tissues and cells is required.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Integrated Traditional Chinese and Western Medicine and Rheumatology, Dianjiang People’s Hospital of Chongqing , ,",
    "Department of Traditional Chinese Medicine, Yongxing Town Central Health Center , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Lin Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Ling Cheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Jin He"
    },
    {
      "affs": [
        1
      ],
      "name": "Rui Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xia Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Qiurong Xia"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a1m5qspfz8dm7.bib",
  "cited_by": 0,
  "doi": "10.3389/fcell.2026.1951682",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13719448/?tool=EBI",
  "id": "a1m5qspfz8dm7",
  "issns": [
    "2296-634X"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13719448",
  "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",
      "Original Research"
    ],
    [
      "openalex",
      "2746|Shoulder Injury and Treatment"
    ]
  ],
  "openalex": "W7222645960",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13719448/pdf/?tool=EBI",
  "pmcid": "PMC13719448",
  "pmid": "42964210",
  "published": "2026-10-16",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/a1m5qspfz8dm7.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:36Z",
      "native_id": "PMC:PMC13719448",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13719448"
    },
    {
      "first_seen": "2026-11-02T12:23:24Z",
      "native_id": "PMC13719448",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fcell.2026.1951682"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2746|Shoulder Injury and Treatment",
      "subfield": "surgery"
    }
  ],
  "title": "Extracellular matrix remodeling and regulated cell-death-immune associations in adhesive capsulitis: a three-cohort transcriptomic analysis",
  "title_text": "Extracellular matrix remodeling and regulated cell-death-immune associations in adhesive capsulitis: a three-cohort transcriptomic analysis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:20:30Z",
  "url": "https://research.draconitic.com/paper/a1m5qspfz8dm7",
  "venue": "Frontiers in cell and developmental biology",
  "versions": []
}