{
  "abstract": "Background\n\nTobacco exposure contributes to the development and progression of head and neck squamous cell carcinoma (HNSCC) through genomic damage and alterations in the tumor microenvironment. Cancer-associated fibroblasts (CAFs) are important stromal components of the tumor microenvironment, but the relationships among smoking background, CAF-related transcriptional programs, and clinical outcomes in HNSCC remain incompletely understood. We aimed to characterize CAF-related transcriptional programs in HNSCC and evaluate their prognostic relevance in the context of smoking status.Methods\n\nWe integrated scRNA-seq data with bulk RNA-seq analyses from TCGA-HNSC, in which smoking-background differential expression analyses were used for candidate-gene discovery. Using hdWGCNA, we identified CAF-associated gene modules and constructed a smoking-related CAF 11-gene (SRCAF-11) signature using machine-learning approaches. We evaluated the signature using external cohorts, immune deconvolution analyses, and SHAP-based feature interpretation. We also modulated INHBA expression in HNSCC cell lines to assess its effects on proliferation, migration, invasion, and EMT-related features.Results\n\nWe identified five transcriptionally distinct CAF subtypes. Matrix-remodeling CAFs (matCAFs) showed extracellular matrix-related features, and higher MuSiC-inferred matCAF relative abundance was associated with poorer survival. Smoker and non-smoker tumors did not differ significantly in MuSiC-inferred CAF-subtype proportions, whereas smoker tumors showed enrichment of EMT- and extracellular matrix-remodeling-related transcriptional programs. The SRCAF-11 signature stratified overall survival across retrospective HNSCC cohorts. INHBA emerged as a major contributor to the model and was preferentially expressed in matCAFs. High INHBA expression was associated with lower inferred immune activity and increased EMT-related transcriptional features in malignant epithelial cells. In vitro, modulation of INHBA expression altered HNSCC cell proliferation, migration, invasion, epithelial and mesenchymal marker expression, and E-cadherin localization.Conclusion\n\nThe SRCAF-11 signature showed prognostic stratification capability across retrospective HNSCC cohorts. INHBA was identified as a major model feature associated with p-EMT-related transcriptional characteristics. These findings support a context-dependent association between smoking status, CAF-related transcriptional programs, and aggressive tumor phenotypes in HNSCC. Further mechanistic and spatial validation is required.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Otorhinolaryngology-Head and Neck Surgery, Peking University People's Hospital, No.11 Xizhimen South Street, Beijing, China.",
    "Department of Otorhinolaryngology-Head and Neck Surgery, Peking University People's Hospital, No.11 Xizhimen South Street, Beijing, China. zhaoyixin16@163.com."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Tao Shi"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuqing Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Lisheng Yu"
    },
    {
      "affs": [
        1
      ],
      "name": "Yixin Zhao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4ms33pxhpw54s.bib",
  "cited_by": 0,
  "doi": "10.1186/s12885-026-16603-0",
  "fulltext_url": "https://europepmc.org/articles/PMC13726021",
  "id": "4ms33pxhpw54s",
  "issns": [
    "1471-2407"
  ],
  "landing_url": "https://europepmc.org/article/MED/42972293",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2733|Head and Neck Cancer Studies"
    ]
  ],
  "openalex": "W7172439653",
  "pdf_url": "https://europepmc.org/articles/PMC13726021?pdf=render",
  "pmcid": "PMC13726021",
  "pmid": "42972293",
  "published": "2026-08-05",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/4ms33pxhpw54s.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T15:20:49Z",
      "native_id": "MED:42972293",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42972293"
    },
    {
      "first_seen": "2026-11-05T12:22:26Z",
      "native_id": "PMC13726021",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s12885-026-16603-0"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2733|Head and Neck Cancer Studies",
      "subfield": "general"
    }
  ],
  "title": "Multi-omics characterization of CAF-related transcriptional programs reveals a smoking-context-informed 11-gene prognostic signature in HNSCC.",
  "title_text": "Multi-omics characterization of CAF-related transcriptional programs reveals a smoking-context-informed 11-gene prognostic signature in HNSCC.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:22:04Z",
  "url": "https://research.draconitic.com/paper/4ms33pxhpw54s",
  "venue": "BMC cancer",
  "versions": []
}