{
  "id": 18056509,
  "title": "Quantitative Donor Histology and Transcriptomics Link Pancreatic Composition and Precancers Across the Adult Lifespan",
  "url": "https://urgent.news/2026/11/03/quantitative-donor-histology-and-transcriptomics-link-pancreatic",
  "topic": "science",
  "section": "Science",
  "published": "2026-11-03T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.10.30.763196v1?rss=1"
  },
  "original_language": "en",
  "account": "Background and Objectives: Pancreatic intraepithelial neoplasia (PanIN) serves as the initial stage for invasive pancreatic ductal adenocarcinoma (PDAC). Although PanIN is prevalent among adults, PDAC remains uncommon. Research has indicated that the risk of PDAC increases with age, diabetes mellitus, and obesity, but it remains unclear if this heightened risk is due to a higher prevalence of precancerous cells, as prior studies primarily focused on PanIN presence and grade. The present study aimed to quantify pancreatic composition and PanIN burden throughout the adult lifespan to uncover demographics with an excessive precancer burden.\n\nMethodology: Researchers utilized CODAvision, a deep-learning segmentation pipeline, to analyze 410 high-quality pancreas sections from Genotype-Tissue Expression (GTEx) donors aged between 21 and 70 years. The analysis encompassed 27 donor phenotypes against 14 compositional measures, with Benjamini-Hochberg correction applied to account for multiple testing. Furthermore, tissue composition and donor phenotype were correlated with bulk gene expression in 281 donors to determine which demographics exhibit a compositional or transcriptional fingerprint.\n\nFindings: PanIN was observed in 83% of the donors. Acinar proportion decreased with age, counterbalanced by increases in fat and stroma. While the median PanIN burden remained stable with age, the 90th percentile increased from 0.21% to 0.72% of exocrine tissue (uncorrected P=.002). Ten percent of the analyzed sections (39 sections) showed high-outlier PanIN burden, predominantly originating from donors with type 2 diabetes mellitus and hypertension. Additionally, these donors exhibited greater stromal proportion and higher densities of fibroblasts and immune cells in both peri-PanIN stroma and surrounding pancreatic parenchyma. Furthermore, PanIN abundance correlated with a gastric transcriptional signature, encompassing genes such as VSIG1, TFF1, and MUC5AC.\n\nConclusion: The vast majority of donors harbored minimal PanIN throughout their adult lives, while a minority of donors exhibited high burden, predominantly characterized by type 2 diabetes mellitus, hypertension, and inflamed, fibrotic stroma. Despite PanIN being present in the majority of donors, its presence was insufficient to distinguish high-risk groups. Conversely, the quantitative burden of PanIN did, concentrating within the metabolic phenotypes that are already under consideration for pancreatic surveillance.",
  "summary": "Background & Aims: Pancreatic intraepithelial neoplasia (PanIN) is the primary precursor to invasive pancreatic ductal adenocarcinoma (PDAC). While PanIN is common in the general population, PDAC is rare. PDAC risk rises with age, diabetes mellitus, and obesity, but whether this increased risk reflects a greater precancer burden is unknown, as previous studies assessed PanIN presence and grade.…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}