title: Prospective validation of microRNA signatures for detecting pancreatic malignant transformation in endoscopic-ultrasound guided fine-needle aspiration biopsies.
abstract: BACKGROUND
  Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. Novel biomarkers are required to aid treatment decisions and improve patient outcomes. MicroRNAs (miRNAs) are potentially ideal diagnostic biomarkers, as they are stable molecules, and tumour and tissue specific.
  
  
  RESULTS
  Logistic regression analysis revealed an endoscopic-ultrasound fine-needle aspiration (EUS-FNA) 2-miRNA classifier (miR-21 + miR-155) capable of distinguishing benign from malignant pancreatic lesions with a sensitivity of 81.5% and a specificity of 85.7% (AUC 0.930). Validation FNA cohorts confirmed both miRNAs were overexpressed in malignant disease, while circulating miRNAs performed poorly.
  
  
  METHODS
  Fifty-five patients with a suspicious pancreatic lesion on cross-sectional imaging were evaluated by EUS-FNA. At echo-endoscopy, the first part of the FNA was sent for cytological assessment and the second part was used for total RNA extraction. Candidate miRNAs were selected after careful review of the literature and expression was quantified by qRT-PCR. Validation was performed on an independent cohort of EUS-FNAs, as well as formalin-fixed paraffin embedded (FFPE) and plasma samples.
  
  
  CONCLUSIONS
  We provide further evidence for using miRNAs as diagnostic biomarkers for pancreatic malignancy. We demonstrate the feasibility of using fresh EUS-FNAs to establish miRNA-based signatures unique to pancreatic malignant transformation and the potential to enhance risk stratification and selection for surgery.
authors.affiliation: HPB Surgical Unit, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, UK.|Division of Cancer, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, UK.
authors.forename: Adam E
authors.initials: AE
authors.lastname: Frampton
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Krell
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, UK.
authors.forename: Mireia Mato
authors.initials: MM
authors.lastname: Prado
authors.affiliation: HPB Surgical Unit, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, UK.
authors.forename: Tamara M H
authors.initials: TM
authors.lastname: Gall
authors.affiliation: Academic Surgical Unit, Department of Surgery and Cancer, Imperial College, St. Mary's Hospital, London, UK.
authors.forename: Nima
authors.initials: N
authors.lastname: Abbassi-Ghadi
authors.affiliation: Department of Systems Medicine, Gastroenterology Unit, University Tor Vergata, Rome, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Del Vecchio Blanco
authors.affiliation: Cancer Pharmacology Lab, AIRC Start-Up Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.|CNR-Nano, Institute of Nanoscience and Nanotechnology, Pisa, Italy.
authors.forename: Niccola
authors.initials: N
authors.lastname: Funel
authors.affiliation: Cancer Pharmacology Lab, AIRC Start-Up Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.|CNR-Nano, Institute of Nanoscience and Nanotechnology, Pisa, Italy.|Department of Medical Oncology, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Elisa
authors.initials: E
authors.lastname: Giovannetti
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, UK.
authors.forename: Leandro
authors.initials: L
authors.lastname: Castellano
authors.affiliation: HPB Surgical Unit, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, UK.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Basyouny
authors.affiliation: HPB Surgical Unit, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, UK.
authors.forename: Nagy A
authors.initials: NA
authors.lastname: Habib
authors.affiliation: Department of Gastroenterology, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK.
authors.forename: Harry
authors.initials: H
authors.lastname: Kaltsidis
authors.affiliation: Department of Gastroenterology, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Vlavianos
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, UK.
authors.forename: Justin
authors.initials: J
authors.lastname: Stebbing
authors.affiliation: HPB Surgical Unit, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, UK.
authors.forename: Long R
authors.initials: LR
authors.lastname: Jiao
mesh_terms: D000328:Adult; D000368:Aged; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D061765:Endoscopic Ultrasound-Guided Fine Needle Aspiration / Q000379:methods*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016015:Logistic Models; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D011446:Prospective Studies; D012680:Sensitivity and Specificity
chemical_list: C524942:MIRN155 microRNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs
keywords: endoscopic ultrasound (EUS); fine-needle aspiration (FNA); microRNA; pancreatic cyst; pancreatic ductal adenocarcinoma