title: Specific MAPK-Associated MicroRNAs in Serum Differentiate Pancreatic Cancer from Autoimmune Pancreatitis.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is difficult to distinguish from autoimmune pancreatitis (AIP) because of their clinical and radiological similarities, and therefore simple and minimally invasive surrogate markers for differential diagnosis would be useful. In our previous studies, we identified four microRNAs (miRNAs)-miR-7, miR-34a, miR-181d, and miR-193b -as MAPK-associated microRNAs whose expression was altered significantly with upregulation of the MAPK signaling pathway. Recently it has been reported that these miRNAs could be used as biomarkers in serum samples for accurate diagnosis of pancreatic lesions. The aim of the present study was to evaluate whether these MAPK-associated miRNAs in serum could be used as biomarkers for differentiating PDAC from AIP. We enrolled 69 patients with PDAC, 26 with intraductal papillary mucinous neoplasm (IPMN) and 15 with AIP. The expression of MAPK-associated miRNAs in serum was measured by quantitative real-time PCR. The 2-ΔCT method was used to quantify the expression of miRNAs, and the data were normalized using spiked-in synthetic cel-miR-39. Patients with PDAC or IPMN showed significantly higher amounts of serum MAPK-associated miRNAs than those with AIP (p<0.009 for miR-7, p<0.002 for miR-34a, p<0.001 for miR-181d, p<0.002 for miR-193b). ROC curve analysis demonstrated that these miRNAs had an area under the ROC curve (AUC) of 0.723-0.882 for differentiation between PDAC or IPMN from AIP. Furthermore, serum miR-181d was significantly associated with the presence of metastasis in patients with PDA (p = 0.014). Serum MAPK-associated miRNAs could be novel noninvasive biomarkers for differentiation between PDAC or IPMN and AIP.
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan.
authors.forename: Manabu
authors.identifier: http://orcid.org/0000-0003-0719-1463
authors.initials: M
authors.lastname: Akamatsu
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Makino
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan.
authors.forename: Yushi
authors.initials: Y
authors.lastname: Ikeda
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Matsuda
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Kakizaki
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ishizawa
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Institute for Integrated Medical Sciences, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Furukawa
authors.affiliation: Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ueno
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001327:Autoimmune Diseases / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D010195:Pancreatitis / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; C546818:MIRN193 microRNA, human; C522425:MIRN34 microRNA, human; C549242:MIRN7-1 microRNA, human; C540193:MIrn181 microRNA, human