title: MicroRNA molecular profiles associated with diagnosis, clinicopathologic criteria, and overall survival in patients with resectable pancreatic ductal adenocarcinoma.
abstract: OBJECTIVE
  MicroRNAs (miRNA) have potential as diagnostic and prognostic biomarkers and as therapeutic targets in cancer. We sought to establish the relationship between miRNA expression and clinicopathologic parameters, including prognosis, in pancreatic ductal adenocarcinoma (PDAC).
  
  
  METHODS
  Global miRNA microarray expression profiling of prospectively collected fresh-frozen PDAC tissue was done on an initial test cohort of 48 patients, who had undergone pancreaticoduodenectomy between 2003 and 2008 at a single institution. We evaluated association with tumor stage, lymph node status, and site of recurrence, in addition to overall survival, using Cox regression multivariate analysis. Validation of selected potentially prognostic miRNAs was done in a separate cohort of 24 patients.
  
  
  RESULTS
  miRNA profiling identified expression signatures associated with PDAC, lymph node involvement, high tumor grade, and 20 miRNAs were associated with overall survival. In the initial cohort of 48 PDAC patients, high expression of miR-21 (HR = 3.22, 95% CI: 1.21-8.58) and reduced expression of miR-34a (HR = 0.15, 95% CI: 0.06-0.37) and miR-30d (HR = 0.30, 95% CI: 0.12-0.79) were associated with poor overall survival following resection independent of clinical covariates. In a further validation set of 24 patients, miR-21 and miR-34a expression again significantly correlated with overall survival (P = 0.031 and P = 0.001).
  
  
  CONCLUSIONS
  Expression patterns of miRNAs are significantly altered in PDAC. Aberrant expression of a number of miRNAs was independently associated with reduced survival, including overexpression of miR-21 and underexpression of miR-34a.
  
  
  CONCLUSIONS
  miRNA expression profiles for resected PDAC were examined to identify potentially prognostic miRNAs. miRNA microarray analysis identified statistically unique profiles, which could discriminate PDAC from paired nonmalignant pancreatic tissues as well as molecular signatures that differ according to pathologic features. miRNA expression profiles correlated with overall survival of PDAC following resection, indicating that miRNAs provide prognostic utility.
authors: West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Alexandra Parade, Glasgow, G31 2ER, United Kingdom. nigeljamieson@yahoo.com
authors: Nigel B
authors: NB
authors: Jamieson
authors: Douglas C
authors: DC
authors: Morran
authors: Jennifer P
authors: JP
authors: Morton
authors: Asif
authors: A
authors: Ali
authors: Euan J
authors: EJ
authors: Dickson
authors: C Ross
authors: CR
authors: Carter
authors: Owen J
authors: OJ
authors: Sansom
authors: T R Jeffry
authors: TR
authors: Evans
authors: Colin J
authors: CJ
authors: McKay
authors: Karin A
authors: KA
authors: Oien
mesh_terms: D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D015331:Cohort Studies; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D020411:Oligonucleotide Array Sequence Analysis; D010179:Pancreas / Q000378:metabolism; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: C524940:MIRN21 microRNA, human; C522425:MIRN34 microRNA, human; D035683:MicroRNAs