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MiR-10a in Pancreatic Juice as a Biomarker for Invasive Intraductal Papillary Mucinous Neoplasm by miRNA Sequencing
Authors:Natsuhiko Kuratomi  Shinichi Takano  Mitsuharu Fukasawa  Shinya Maekawa  Makoto Kadokura  Hiroko Shindo  Ei Takahashi  Sumio Hirose  Yoshimitsu Fukasawa  Satoshi Kawakami  Hiroshi Hayakawa  Hitomi Takada  Natsuko Nakakuki  Ryoh Kato  Tatsuya Yamaguchi  Yasuhiro Nakayama  Hiromichi Kawaida  Hiroshi Kono  Taisuke Inoue  Tetsuo Kondo  Daisuke Ichikawa  Nobuyuki Enomoto
Affiliation:1.First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan; (N.K.); (M.F.); (S.M.); (M.K.); (H.S.); (E.T.); (S.H.); (Y.F.); (S.K.); (H.H.); (H.T.); (N.N.); (R.K.); (T.Y.); (Y.N.); (T.I.); (N.E.);2.First Department of Surgery, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan; (H.K.); (H.K.); (D.I.);3.Department of Pathology, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan;
Abstract:New biomarkers are needed to further stratify the risk of malignancy in intraductal papillary mucinous neoplasm (IPMN). Although microRNAs (miRNAs) are expected to be stable biomarkers, they can vary owing to a lack of definite internal controls. To identify universal biomarkers for invasive IPMN, we performed miRNA sequencing using tumor-normal paired samples. A total of 19 resected tissues and 13 pancreatic juice samples from 32 IPMN patients were analyzed for miRNA expression by next-generation sequencing with a two-step normalization of miRNA sequence data. The miRNAs involved in IPMN associated with invasive carcinoma were identified from this tissue analysis and further verified with the pancreatic juice samples. From the tumor-normal paired tissue analysis of the expression levels of 2792 miRNAs, 20 upregulated and 17 downregulated miRNAs were identified. In IPMN associated with invasive carcinoma (INV), miR-10a-5p and miR-221-3p were upregulated and miR-148a-3p was downregulated when compared with noninvasive IPMN. When these findings were further validated with pancreatic juice samples, miR-10a-5p was found to be elevated in INV (p = 0.002). Therefore, three differentially expressed miRNAs were identified in tissues with INV, and the expression of miR-10a-5p was also elevated in pancreatic juice samples with INV. MiR-10a-5p is a promising additional biomarker for invasive IPMN.
Keywords:intraductal papillary mucinous neoplasm   miRNA   pancreatic juice   formalin-fixed paraffin-embedded samples   next-generation sequencing
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