title: microRNAs with prognostic significance in pancreatic ductal adenocarcinoma: A meta-analysis.
abstract: BACKGROUND
  Reports have described the prognostic relevance of microRNAs (miRNAs) in patients treated for pancreatic ductal adenocarcinoma (PDAC). However, many of these include small numbers of patients. To increase statistical power and improve translation, we performed a systematic review and meta-analysis to determine a pooled conclusion. We examined the impact of miRNAs on overall survival (OS) and disease-free survival (DFS) in PDAC.
  
  
  METHODS
  Eligible studies were identified and quality assessed using multiple search strategies (last search December 2014). Data were collected from studies correlating clinical outcomes with dysregulated tumoural or blood miRNAs. Studies were pooled, and combined hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate strength of the associations.
  
  
  RESULTS
  Twenty studies involving 1525 patients treated for PDAC were included. After correcting for publication bias, OS was significantly shortened in patients with high tumoural miR-21 (adjusted HR = 2.48; 1.96-3.14). This result persisted when only studies adjusting for adjuvant chemotherapy were combined (adjusted HR = 2.72; 1.91-3.89). High miR-21 also predicted reduced DFS (adjusted HR = 3.08; 1.78-5.33). Similarly, we found significant adjusted HRs for poor OS for high miR-155, high miR-203, and low miR-34a; and unadjusted HRs for high miR-222 and high miR-10b. The small number of studies, limited number of miRNAs and paucity of multivariate analyses are the limitations of our study.
  
  
  CONCLUSIONS
  This is the first rigorous pooled analysis assessing miRNAs as prognostic biomarkers in PDAC. Tumoural miR-21 overexpression emerged as an important predictor of poor prognosis after PDAC resection independent of other clinicopathologic factors, including adjuvant chemotherapy use.
authors.affiliation: HPB Surgical Unit, Division of Surgery, Dept. of Surgery & Cancer, Imperial College, Hammersmith Hospital Campus, Du Cane Road, London W12 0HS, UK; Division of Oncology, Dept. of Surgery & Cancer, Imperial Centre for Translational and Experimental Medicine (ICTEM), Imperial College, Hammersmith Hospital campus, Du Cane Road, London W12 0NN, UK. Electronic address: a.frampton@imperial.ac.uk.
authors.forename: Adam E
authors.initials: AE
authors.lastname: Frampton
authors.affiliation: Division of Oncology, Dept. of Surgery & Cancer, Imperial Centre for Translational and Experimental Medicine (ICTEM), Imperial College, Hammersmith Hospital campus, Du Cane Road, London W12 0NN, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Krell
authors.affiliation: Academic Unit of Surgery, Faculty of Medicine, Glasgow Royal Infirmary, Alexandra Parade, University of Glasgow, G31 2ER, UK.
authors.forename: Nigel B
authors.initials: NB
authors.lastname: Jamieson
authors.affiliation: HPB Surgical Unit, Division of Surgery, Dept. of Surgery & Cancer, Imperial College, Hammersmith Hospital Campus, Du Cane Road, London W12 0HS, UK.
authors.forename: Tamara M H
authors.initials: TM
authors.lastname: Gall
authors.affiliation: Dept. of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Elisa
authors.initials: E
authors.lastname: Giovannetti
authors.affiliation: Dept. of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Italy.
authors.forename: Niccola
authors.initials: N
authors.lastname: Funel
authors.affiliation: Division of Oncology, Dept. of Surgery & Cancer, Imperial Centre for Translational and Experimental Medicine (ICTEM), Imperial College, Hammersmith Hospital campus, Du Cane Road, London W12 0NN, UK.
authors.forename: Mireia
authors.initials: M
authors.lastname: Mato Prado
authors.affiliation: Dept. of Academic Oncology, Royal Free Hospital, Pond Street, London NW3 2QG, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Krell
authors.affiliation: HPB Surgical Unit, Division of Surgery, Dept. of Surgery & Cancer, Imperial College, Hammersmith Hospital Campus, Du Cane Road, London W12 0HS, UK.
authors.forename: Nagy A
authors.initials: NA
authors.lastname: Habib
authors.affiliation: Division of Oncology, Dept. of Surgery & Cancer, Imperial Centre for Translational and Experimental Medicine (ICTEM), Imperial College, Hammersmith Hospital campus, Du Cane Road, London W12 0NN, UK.
authors.forename: Leandro
authors.initials: L
authors.lastname: Castellano
authors.affiliation: HPB Surgical Unit, Division of Surgery, Dept. of Surgery & Cancer, Imperial College, Hammersmith Hospital Campus, Du Cane Road, London W12 0HS, UK.
authors.forename: Long R
authors.initials: LR
authors.lastname: Jiao
authors.affiliation: Division of Oncology, Dept. of Surgery & Cancer, Imperial Centre for Translational and Experimental Medicine (ICTEM), Imperial College, Hammersmith Hospital campus, Du Cane Road, London W12 0NN, UK. Electronic address: j.stebbing@imperial.ac.uk.
authors.forename: Justin
authors.initials: J
authors.lastname: Stebbing
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs
keywords: Biomarker; Meta-analysis; Pancreatic cancer; Prognosis; miR-21; microRNAs