{
  "abstract": "Background No clinically useful non-invasive biomarkers have been developed for diagnosis of chronic pancreatitis (CP), and molecular features of CP have not been characterised. Extracellular vesicles (EVs) consisted of abundant RNA species with specialised functions and clinical applications.Objective Our study aimed to construct a diagnostic model for CP and depict molecular landscape of CP based on EV long RNA (ExLR).Design Candidate ExLRs were defined using prespecified expression-quality criteria and complementary discovery-stage screens, and a resampling-based consensus feature selection in the training cohort yielded a five-ExLRs panel for model construction. The ExLRs-based CP diagnostic model (ExLRCPdscore) was further confirmed in another two independent validation cohorts with different controls. To elucidate the biological architecture of CP through ExLR profiling, we integrated ExLR-seq, single-cell data and clinical information.Results ExLRCPdscore constructed by random forest demonstrated excellent performance for detecting CP. Importantly, ExLRCPdscore could effectively detect early-stage CP, CP without alarm symptoms, CP without significant imaging findings and CP without risk factors. Using ExLR profiling and phenotypic data, we pinpointed MUC5B + ductal cells exhibiting the strongest correlation with CP and derived an ExLR-based acinar-to-ductal metaplasia (ADM) score as a blood-based transcriptomic proxy of ADM-related programme. Integration of ExLR-seq and clinical information revealed significant associations between ADMscore and clinical characteristics, imaging findings and metabolic sequelae.Conclusion Our study is the first to report an ExLRs-based diagnostic model that demonstrates exceptional robustness in differentiating CP from healthy controls and non-pancreatic disease controls. ExLRs offer a promising tool for CP molecular characterisation and pathophysiological quantification.",
  "authors": [
    {
      "affiliations": [
        "National Clinical Research Center for Digestive Diseases, Department of Gastroenterology, Changhai Hospital, National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China",
        "Shanghai Institute of Pancreatic Diseases, Shanghai, China"
      ],
      "name": "Yu Cao"
    },
    {
      "affiliations": [
        "International Co-laboratory of Medical Epigenetics and Metabolism, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, China",
        "Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China"
      ],
      "name": "Jia Hu"
    },
    {
      "affiliations": [
        "National Clinical Research Center for Digestive Diseases, Department of Gastroenterology, Changhai Hospital, National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China",
        "Shanghai Institute of Pancreatic Diseases, Shanghai, China"
      ],
      "name": "Jun Ye"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"
      ],
      "name": "Duowu Zou"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China",
        "Pancreatic Disease Center of Xi’an Jiaotong University, Xi’an, Shaanxi, China"
      ],
      "name": "Zheng Wang"
    },
    {
      "affiliations": [
        "Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China"
      ],
      "name": "Tao Yin"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China",
        "Pancreatic Disease Center of Xi’an Jiaotong University, Xi’an, Shaanxi, China"
      ],
      "name": "Wanxing Duan"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases, Changhai Hospital, Naval Medical University, Shanghai, China"
      ],
      "name": "Xuesong Liang"
    },
    {
      "affiliations": [
        "International Co-laboratory of Medical Epigenetics and Metabolism, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, China",
        "Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China"
      ],
      "name": "Jinying Chen"
    },
    {
      "affiliations": [
        "International Co-laboratory of Medical Epigenetics and Metabolism, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, China",
        "Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China"
      ],
      "name": "Yuchen Li"
    },
    {
      "affiliations": [
        "International Co-laboratory of Medical Epigenetics and Metabolism, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, China",
        "Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China"
      ],
      "name": "Hongyan Lai"
    },
    {
      "affiliations": [
        "Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, China"
      ],
      "name": "Shulin Yu"
    },
    {
      "affiliations": [
        "International Co-laboratory of Medical Epigenetics and Metabolism, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, China",
        "Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China"
      ],
      "name": "Zhen Wang"
    },
    {
      "affiliations": [
        "National Clinical Research Center for Digestive Diseases, Department of Gastroenterology, Changhai Hospital, National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China",
        "Shanghai Institute of Pancreatic Diseases, Shanghai, China"
      ],
      "name": "Yahui Wang"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Oncology, Zhongshan Hospital, Fudan University, Shanghai, China"
      ],
      "name": "Peng Wang"
    },
    {
      "affiliations": [
        "National Clinical Research Center for Digestive Diseases, Department of Gastroenterology, Changhai Hospital, National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China",
        "Shanghai Institute of Pancreatic Diseases, Shanghai, China"
      ],
      "name": "Zhaoshen Li"
    },
    {
      "affiliations": [
        "National Clinical Research Center for Digestive Diseases, Department of Gastroenterology, Changhai Hospital, National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China",
        "Shanghai Institute of Pancreatic Diseases, Shanghai, China"
      ],
      "name": "Wenbin Zou"
    },
    {
      "affiliations": [
        "International Co-laboratory of Medical Epigenetics and Metabolism, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, China",
        "Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China"
      ],
      "name": "Shenglin Huang"
    },
    {
      "affiliations": [
        "National Clinical Research Center for Digestive Diseases, Department of Gastroenterology, Changhai Hospital, National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China",
        "Shanghai Institute of Pancreatic Diseases, Shanghai, China"
      ],
      "name": "Zhuan Liao"
    }
  ],
  "title": "Circulating extracellular vesicle long RNA profiling combined with machine learning unveils novel diagnostic signature and molecular features in chronic pancreatitis",
  "uid": "7de13305-e1da-59cc-b4fa-b0c09ccfcbae"
}