{
  "abstract": "Pancreatic ductal adenocarcinoma (PDAC) arises within an extensively remodeled microenvironment, yet tissue markers that distinguish invasive carcinoma from precursor lesions remain limited. Integrating four single-cell RNA-sequencing atlases comprising 324,662 cells from 26 patients, we identified cancer-associated fibroblast expansion, accumulation of C1QA+ immunoregulatory macrophages, and depletion of a dendritic-cell compartment expressing plasmacytoid markers. Fibroblasts were enriched for extracellular-matrix and PI3K-AKT programs and macrophages for an antigen-presentation program. We then examined the protein-level correlates of these populations in a tissue proteomic reference framework of 356 samples spanning non-diseased pancreas, normal-adjacent tissue, low- and high-grade intraductal papillary mucinous neoplasms (IPMNs), IPMN-associated invasive carcinoma, and PDAC, prioritizing proteins that changed monotonically across the six histopathologic reference groups or marked tumor-enriched cell types. Despite depletion of plasmacytoid dendritic cells, the principal source of type I interferon, the interferon-stimulated protein ISG15, expressed by both fibroblasts and macrophages, increased monotonically toward PDAC. In exploratory cross-validated benchmarking of PDAC versus low- and high-grade IPMN, excluding IPMN-associated invasive carcinoma (145 versus 56 samples), CATB+EPIPL achieved an AUC of 0.98, with a sensitivity of 92% at an achieved specificity of 92%, exceeding protein-abundance models of diagnostic IHC-associated markers (S100P+IMP3+maspin+MSLN, 0.79) and refitted published IPMN-progression combinations ([≤]0.91). Against non-diseased pancreas, candidate and comparator panels performed similarly (AUC 0.99-1.00). These biologically informed tissue protein panels warrant independent validation, including immunohistochemical evaluation of EUS-guided fine-needle biopsy specimens and measurement in blood.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Surgery, Indiana University School of Medicine"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "T. T. Tran"
    },
    {
      "name": "P. U. Nguyen Hoang"
    },
    {
      "name": "D. T. Pham"
    },
    {
      "name": "J. Fahrmann"
    },
    {
      "name": "L. Bui"
    },
    {
      "name": "N. H. Bui"
    },
    {
      "name": "C. M. Schmidt"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6y09h8rvabfec.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.02.26364030",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.10.02.26364030v1.full",
  "id": "6y09h8rvabfec",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.10.02.26364030v1",
  "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",
      "gastroenterology"
    ],
    [
      "openalex",
      "2730|Pancreatic and Hepatic Oncology Research"
    ]
  ],
  "openalex": "W7220982153",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.10.02.26364030v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-02",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6y09h8rvabfec.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:20Z",
      "native_id": "10.64898/2026.10.02.26364030",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.10.02.26364030v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Pancreatic and Hepatic Oncology Research",
      "subfield": "oncology"
    }
  ],
  "title": "Integrated single-cell and proteomic profiling of pancreatic neoplasia identifies tissue markers that outperform established diagnostic markers in distinguishing cancer from precursor lesions.",
  "title_text": "Integrated single-cell and proteomic profiling of pancreatic neoplasia identifies tissue markers that outperform established diagnostic markers in distinguishing cancer from precursor lesions.",
  "type": "preprint",
  "updated_at": "2026-10-30T12:20:20Z",
  "url": "https://research.draconitic.com/paper/6y09h8rvabfec",
  "venue": "medRxiv",
  "versions": []
}