{
  "abstract": "Background: Pancreatic ductal adenocarcinoma (PDAC) develops within a complex tumor microenvironment characterized by malignant epithelial states, myeloid inflammation, and coagulation abnormalities. Related thrombo-inflammatory transcriptional features have also been observed in ischemic stroke, but whether these diseases share reproducible molecular programs, and how such programs are organized across cellular compartments in PDAC, remains incompletely understood.\n\nMethods: We integrated transcriptomic datasets from three ischemic stroke cohorts and two paired PDAC tumor–normal cohorts using within-cohort modeling and random-effects meta-analysis. Candidate programs were subsequently investigated using independent bulk transcriptomic, single-cell RNA-sequencing, paired proteomic, spatial transcriptomic, clinical, and human genetic datasets to assess their reproducibility, cellular localization, tumor-microenvironment context, and translational relevance.\n\nResults: Iterative quality-control and replication filters identified 46 concordantly altered genes across the analyzed PDAC and ischemic stroke datasets. Six sentinel genes organized this cross-disease transcriptional signal into an epithelial program comprising CEACAM6, ANXA3, and IL1RAP; a myeloid program comprising TREM1 and IL1R2; and a coagulation-associated component represented by F5. All six genes were independently validated in PDAC, while 34 of 36 quantifiable candidate pairs showed concordant transcript–protein changes. Single-cell and spatial analyses localized the epithelial and myeloid programs to distinct malignant and immune compartments within the PDAC microenvironment. After adjustment for inferred cell abundance, the epithelial program remained the most reproducible cross-disease transcriptional feature, whereas the myeloid and coagulation-associated programs showed greater dependence on cellular composition and disease context. External stroke validation was heterogeneous, and survival, protein quantitative trait locus, and colocalization analyses did not support independent prognostic or genetic-causal interpretations.\n\nConclusion: This multi-omic study defines a compartment-resolved cellular framework in PDAC characterized by a stable tumor-associated epithelial program and more context-dependent myeloid and coagulation-associated programs identified through cross-disease analysis with ischemic stroke. These findings provide a mechanistically informed framework for understanding cancer cell–microenvironment relationships and prioritize CEACAM6, ANXA3, IL1RAP, and TREM1 for functional investigation. They should not be interpreted as evidence that these PDAC-associated programs directly cause or mediate ischemic stroke.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China",
    "School of Pharmacy, Tianjin Medical University, Tianjin, China",
    "Department of Thoracic Surgical Oncology, Shanghai Chest Hospital, Shanghai Institute of Thoracic Oncology, Shanghai Jiao Tong University School of Medicine, Shanghai, China",
    "Department of Lung Cancer Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Lung Cancer Center, Tianjin, China",
    "Second Clinical Medical College, Tianjin Medical University, Tianjin, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hongyan Lu"
    },
    {
      "affs": [
        1
      ],
      "name": "Xiaoqi Qi"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Mengzhe Zhang"
    },
    {
      "affs": [
        4
      ],
      "name": "Haoran Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Ming Zou"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f13d2f1hsyhdy.bib",
  "cited_by": 0,
  "doi": "10.3389/fcell.2026.1969947",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13731346/",
  "id": "f13d2f1hsyhdy",
  "issns": [
    "2296-634X"
  ],
  "landing_url": "https://doi.org/10.3389/fcell.2026.1969947",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2730|Pancreatic and Hepatic Oncology Research"
    ]
  ],
  "openalex": "W7223141610",
  "pdf_url": "https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2026.1969947/pdf",
  "pmcid": "PMC13731346",
  "pmid": "42984787",
  "published": "2026-10-21",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/f13d2f1hsyhdy.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:21:33Z",
      "native_id": "PMC13731346",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fcell.2026.1969947"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Pancreatic and Hepatic Oncology Research",
      "subfield": "oncology"
    }
  ],
  "title": "Compartment-resolved epithelial and myeloid programs are shared by pancreatic ductal adenocarcinoma and ischemic stroke",
  "title_text": "Compartment-resolved epithelial and myeloid programs are shared by pancreatic ductal adenocarcinoma and ischemic stroke",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:21:33Z",
  "url": "https://research.draconitic.com/paper/f13d2f1hsyhdy",
  "venue": "Frontiers in Cell and Developmental Biology",
  "versions": []
}