title: The good, the bad and the ugly: a tale of miR-101, miR-21 and miR-155 in pancreatic intraductal papillary mucinous neoplasms.
abstract: BACKGROUND
  This multicenter study evaluated three candidate microRNAs (miRNAs) (miR-21, miR-155 and miR-101) as potential biomarkers in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas.
  
  
  METHODS
  miRNA expression was quantified by quantitative RT-PCR in 86 laser-microdissected specimens, including 65 invasive IPMNs, 16 non-invasive IPMNs and 5 normal pancreatic ductal tissues. Univariate and multivariate analyses compared miRNAs and clinical parameters with overall (OS) and disease-free survival (DFS).
  
  
  RESULTS
  miR-21 and miR-155 were up-regulated in invasive IPMNs compared with non-invasive IPMNs, as well as in non-invasive IPMNs compared with normal tissues. Conversely, miR-101 levels were significantly higher in non-invasive IPMNs and normal tissues compared with invasive IPMNs. High levels of miR-21 were associated with worse OS [hazard ratio (HR) = 2.47, 95% confidence interval (CI) = 1.37-5.65, P = 0.0047]. Patients with high-miR-21 expression also had a shorter median DFS (10.9 versus 29.9 months, P = 0.01). Multivariate analysis confirmed miR-21 as independently prognostic for mortality and disease progression (death risk: HR = 3.3, 95% CI = 1.5-7.0, P = 0.02; progression risk: HR = 2.3, 95% CI = 1.2-4.8, P = 0.02), as well as positive lymph-node status (death risk: HR = 2.6, 95% CI = 1.1-6.3, P = 0.03; progression risk: HR = 2.2, 95% CI = 1.0-4.8, P = 0.04).
  
  
  CONCLUSIONS
  miR-21, miR-155 and miR-101 showed significant differences in invasive versus non-invasive IPMNs. miR-21 emerged as an independent prognostic biomarker in invasive IPMNs and should be validated in prospective studies.
authors.affiliation: Unit Medical Oncology-2, Azienda Ospedaliero-Universitaria Pisana, Pisa.
authors.forename: S
authors.initials: S
authors.lastname: Caponi
authors.forename: N
authors.initials: N
authors.lastname: Funel
authors.forename: A E
authors.initials: AE
authors.lastname: Frampton
authors.forename: F
authors.initials: F
authors.lastname: Mosca
authors.forename: L
authors.initials: L
authors.lastname: Santarpia
authors.forename: A G
authors.initials: AG
authors.lastname: Van der Velde
authors.forename: L R
authors.initials: LR
authors.lastname: Jiao
authors.forename: N
authors.initials: N
authors.lastname: De Lio
authors.forename: A
authors.initials: A
authors.lastname: Falcone
authors.forename: G
authors.initials: G
authors.lastname: Kazemier
authors.forename: G A
authors.initials: GA
authors.lastname: Meijer
authors.forename: H M
authors.initials: HM
authors.lastname: Verheul
authors.forename: E
authors.initials: E
authors.lastname: Vasile
authors.forename: G J
authors.initials: GJ
authors.lastname: Peters
authors.forename: U
authors.initials: U
authors.lastname: Boggi
authors.forename: E
authors.initials: E
authors.lastname: Giovannetti
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D000231:Adenocarcinoma, Papillary / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016016:Proportional Hazards Models
chemical_list: C534072:MIRN101 microRNA, human; C524942:MIRN155 microRNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs