title: Challenges in detecting pre-malignant pancreatic lesions during acute pancreatitis using a serum microRNA assay: a study based on KrasG12D transgenic mice.
abstract: Caerulein-induced acute pancreatitis accelerates the progression of pancreatic intraepithelial neoplasia (PanIN) lesions in a pancreas-specific KrasG12D mouse model. The purpose of this study was to explore whether serum microRNAs (miRNAs) can serve as sensitive biomarkers to detect occult PanIN in the setting of acute pancreatitis. Serum miRNA profiles were quantified by an array-based method and normalized by both Variance Stabilization Normalization (VSN) and invariant methods. Individual miRNAs were validated by TaqMan real-time PCR with synthetic spike-in C. elegans miRNAs as external controls. Serum miRNA profiles distinguished KrasG12D mice with pancreatitis from wild-type mice without pancreatitis, but failed to differentiate KrasG12D mice with pancreatitis from wild-type mice with pancreatitis. Most individual miRNAs that increased in KrasG12D mice with pancreatitis were not significantly different between KrasG12D mice without pancreatitis and wild-type mice without pancreatitis. Mechanistically, Gene Set Enrichment Analysis (GSEA) of the mRNA array data and immunohistochemical assays showed that caerulein-induced acute pancreatitis involved acinar cell loss and immune cell infiltration, which might contribute to serum miRNA profile changes. This study highlighted the challenges in using sensitive serum miRNA biomarker screening for the early detection of pancreatic malignancies during acute pancreatitis.
authors.affiliation: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
authors.forename: Xiafei
authors.initials: X
authors.lastname: Hong
authors.affiliation: Department of General Surgery, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
authors.forename: Wenze
authors.initials: W
authors.lastname: Wang
authors.affiliation: Center for Bioinformatics, Peking University, Beijing 100871, China.
authors.forename: Adam Yongxin
authors.initials: AY
authors.lastname: Ye
authors.affiliation: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.affiliation: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Dai
authors.affiliation: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
authors.forename: Xianze
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
authors.forename: Lei
authors.initials: L
authors.lastname: You
authors.affiliation: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
authors.forename: Wenming
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
authors.forename: Yupei
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D065311:Adenocarcinoma in Situ / Q000097:blood* / Q000175:diagnosis; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000175:diagnosis; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000097:blood*; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000175:diagnosis; D010195:Pancreatitis / Q000097:blood / Q000150:complications*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)
keywords: KrasG12D; PanIN; miR-210; microRNA; pancreatitis