title: MicroRNAs for Detection of Pancreatic Neoplasia: Biomarker Discovery by Next-generation Sequencing and Validation in 2 Independent Cohorts.
abstract: The aim of our study was to analyze the miRNome of pancreatic ductal adenocarcinoma (PDAC) and its preneoplastic lesion intraductal papillary mucinous neoplasm (IPMN), to find new microRNA (miRNA)-based biomarkers for early detection of pancreatic neoplasia.
  
  
  
  Effective early detection methods for PDAC are needed. miRNAs are good biomarker candidates.
  
  
  
  Pancreatic tissues (n = 165) were obtained from patients with PDAC, IPMN, or from control individuals (C), from Hospital Clínic of Barcelona. Biomarker discovery was done using next-generation sequencing in a discovery set of 18 surgical samples (11 PDAC, 4 IPMN, 3 C). MiRNA validation was carried out by quantitative reverse transcriptase PCR in 2 different set of samples. Set 1-52 surgical samples (24 PDAC, 7 IPMN, 6 chronic pancreatitis, 15 C), and set 2-95 endoscopic ultrasound-guided fine-needle aspirations (60 PDAC, 9 IPMN, 26 C).
  
  
  
  In all, 607 and 396 miRNAs were significantly deregulated in PDAC and IPMN versus C. Of them, 40 miRNAs commonly overexpressed in both PDAC and IPMN were selected for further validation. Among them, significant up-regulation of 31 and 30 miRNAs was confirmed by quantitative reverse transcriptase PCR in samples from set 1 and set 2, respectively.
  
  
  
  miRNome analysis shows that PDAC and IPMN have differential miRNA profiles with respect to C, with a large number of deregulated miRNAs shared by both neoplastic lesions. Indeed, we have identified and validated 30 miRNAs whose expression is significantly increased in PDAC and IPMN lesions. The feasibility of detecting these miRNAs in endoscopic ultrasound-guided fine-needle aspiration samples makes them good biomarker candidates for early detection of pancreatic cancer.
authors.affiliation: *Gastrointestinal & Pancreatic Oncology Group, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)/Hospital Clínic of Barcelona/ Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Catalonia, Spain †Bioinformatics Platform, CIBEREHD/Barcelona, Catalonia, Spain ‡Pathology Department, Hospital Clínic of Barcelona, Barcelona, Catalonia, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Vila-Navarro
authors.forename: Maria
authors.initials: M
authors.lastname: Vila-Casadesús
authors.forename: Leticia
authors.initials: L
authors.lastname: Moreira
authors.forename: Saray
authors.initials: S
authors.lastname: Duran-Sanchon
authors.forename: Rupal
authors.initials: R
authors.lastname: Sinha
authors.forename: Àngels
authors.initials: À
authors.lastname: Ginés
authors.forename: Glòria
authors.initials: G
authors.lastname: Fernández-Esparrach
authors.forename: Rosa
authors.initials: R
authors.lastname: Miquel
authors.forename: Miriam
authors.initials: M
authors.lastname: Cuatrecasas
authors.forename: Antoni
authors.initials: A
authors.lastname: Castells
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Lozano
authors.forename: Meritxell
authors.initials: M
authors.lastname: Gironella
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis*; D002291:Carcinoma, Papillary / Q000175:diagnosis*; D055088:Early Detection of Cancer; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000032:analysis*; D010190:Pancreatic Neoplasms / Q000175:diagnosis*; D011230:Precancerous Conditions / Q000175:diagnosis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs