{
  "abstract": "Background Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions of pancreatic cancer with highly variable malignant potential. Current understanding of their biology remains incomplete, limiting accurate risk stratification and targeted interventions.Objective This study aimed to characterise the molecular and immune features of IPMN across different dysplasia grades and histological subtypes, with a focus on IPMN-associated invasive carcinoma (IPMN-IC).Design Spatial whole-transcriptome profiling using Digital Spatial Profiling was conducted on 12 patients, capturing the full histological and dysplastic spectrum of IPMN and conventional pancreatic ductal adenocarcinoma. A total of 117 epithelial, immune and stromal areas of interest were analysed. An expanded cohort of 43 patients with IPMN was used to validate selected key markers.Results Transcriptomic analysis unveiled stage-specific molecular alterations and identified two distinct subsets of high-grade (HG) IPMN lesions: one resembling indolent lesions (HG) and the other IC (HG+). Key markers associated with divergent biological behaviours were identified, including MUC5AC and TFF1 in indolent lesions, and Claudin-1 in lesions with invasive potential. Immune profiling revealed a trajectory from activation to suppression during IPMN progression. Several characteristic immune checkpoint molecules, including CEACAM1 and CD44, were identified in IPMN-IC.Conclusion This study provides a spatially resolved molecular map of IPMN progression, delineating key transcriptomic and immune signatures. These findings advance the understanding of IPMN biology and highlight potential biomarkers for risk stratification and therapeutic strategies.",
  "authors": [
    {
      "affiliations": [
        "Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"
      ],
      "name": "Ming Cui"
    },
    {
      "affiliations": [
        "Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"
      ],
      "name": "Shengwei Mo"
    },
    {
      "affiliations": [
        "Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"
      ],
      "name": "Jialu Bai"
    },
    {
      "affiliations": [
        "Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, NYU Langone Health, New York, NY, USA"
      ],
      "name": "Ammar A Javed"
    },
    {
      "affiliations": [
        "Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, NYU Langone Health, New York, NY, USA"
      ],
      "name": "Joseph R Habib"
    },
    {
      "affiliations": [
        "Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"
      ],
      "name": "Sen Yang"
    },
    {
      "affiliations": [
        "Biomedical Engineering Facility of National Infrastructures for Translational Medicine, Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"
      ],
      "name": "Tianqi Chen"
    },
    {
      "affiliations": [
        "Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"
      ],
      "name": "Ruiling Xiao"
    },
    {
      "affiliations": [
        "Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"
      ],
      "name": "Wenfei Diao"
    },
    {
      "affiliations": [
        "Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"
      ],
      "name": "Decheng Jiang"
    },
    {
      "affiliations": [
        "Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, NYU Langone Health, New York, NY, USA"
      ],
      "name": "Christopher L Wolfgang"
    },
    {
      "affiliations": [
        "Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"
      ],
      "name": "Xiaoyan Chang"
    },
    {
      "affiliations": [
        "Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"
      ],
      "name": "Ya Hu"
    },
    {
      "affiliations": [
        "Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China",
        "State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"
      ],
      "name": "Yupei Zhao"
    }
  ],
  "title": "Spatial transcriptomics defines the molecular progression, invasion and immune landscape of IPMN and IPMN-derived pancreatic cancer",
  "uid": "a7fb9cd2-be89-5fb4-af27-713a836c7e57"
}