title: Tissue MicroRNA profiles as diagnostic and prognostic biomarkers in patients with resectable pancreatic ductal adenocarcinoma and periampullary cancers.
abstract: BACKGROUND
  The aim of this study was to validate previously described diagnostic and prognostic microRNA expression profiles in tissue samples from patients with pancreatic cancer and other periampullary cancers.
  
  
  METHODS
  Expression of 46 selected microRNAs was studied in formalin-fixed paraffin-embedded tissue from patients with resected pancreatic ductal adenocarcinoma (n= 165), ampullary cancer (n=59), duodenal cancer (n= 6), distal common bile duct cancer (n= 21), and gastric cancer (n= 20); chronic pancreatitis (n= 39); and normal pancreas (n= 35). The microRNAs were analyzed by PCR using the Fluidigm platform.
  
  
  RESULTS
  Twenty-two microRNAs were significantly differently expressed in patients with pancreatic cancer when compared to healthy controls and chronic pancreatitis patients; 17 miRNAs were upregulated (miR-21-5p, -23a-3p, -31-5p, -34c-5p, -93-3p, -135b-3p, -155-5p, -186-5p, -196b-5p, -203, -205-5p, -210, -222-3p, -451, -492, -614, and miR-622) and 5 were downregulated (miR-122-5p, -130b-3p, -216b, -217, and miR-375). MicroRNAs were grouped into diagnostic indices of varying complexity. Ten microRNAs associated with prognosis were identified (let-7 g, miR-29a-5p, -34a-5p, -125a-3p, -146a-5p, -187, -205-5p, -212-3p, -222-5p, and miR-450b-5p). Prognostic indices based on differences in expression of 2 different microRNAs were constructed for pancreatic and ampullary cancer combined and separately (30, 5, and 21 indices).
  
  
  CONCLUSIONS
  The study confirms that pancreatic cancer tissue has a microRNA expression profile that is different from that of other periampullary cancers, chronic pancreatitis, and normal pancreas. We identified prognostic microRNAs and microRNA indices that were associated with shorter overall survival in patients with radically resected pancreatic cancer.
authors.affiliation: Department of Surgical Gastroenterology and Transplantation, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.|Department of Oncology, Herlev University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark.
authors.forename: Dan
authors.identifier: 0000-0002-1844-7404
authors.initials: D
authors.lastname: Calatayud
authors.affiliation: Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Dehlendorff
authors.affiliation: Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
authors.forename: Mogens K
authors.initials: MK
authors.lastname: Boisen
authors.affiliation: Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Jane Preuss
authors.initials: JP
authors.lastname: Hasselby
authors.affiliation: Department of Surgical Gastroenterology and Transplantation, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Nicolai Aagaard
authors.initials: NA
authors.lastname: Schultz
authors.affiliation: Department of General, Visceral, and Transplant Surgery, LMU, University of Munich, Munich, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Werner
authors.affiliation: Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway.|Department of Pathology, Ålesund Hospital, Ålesund, Norway.
authors.forename: Heike
authors.initials: H
authors.lastname: Immervoll
authors.affiliation: Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway.|Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Anders
authors.initials: A
authors.lastname: Molven
authors.affiliation: Department of Surgical Gastroenterology and Transplantation, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Carsten Palnæs
authors.initials: CP
authors.lastname: Hansen
authors.affiliation: Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.|Department of Medicine, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.|Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Julia S
authors.initials: JS
authors.lastname: Johansen
keywords: Ampullary cancer; Biomarkers; Pancreatic cancer; Pancreatic ductal adenocarcinoma; microRNA