title: MiR-score: a novel 6-microRNA signature that predicts survival outcomes in patients with malignant pleural mesothelioma.
abstract: BACKGROUND
  Prognosis of malignant pleural mesothelioma (MPM) is poor, and predicting the outcomes of treatment is difficult. Here we investigate the potential of microRNA expression to estimate prognosis of MPM patients.
  
  
  METHODS
  Candidate microRNAs from microarray profiling of tumor samples from 8 long (median: 53.7 months) and 8 short (median: 6.4 months) survivors following extrapleural pneumonectomy (EPP) were validated by RT-qPCR in 48 additional EPP samples. Kaplan-Meier log ranking was used to further explore the association between microRNA expression and overall survival (OS). Binary logistic regression was used to construct a microRNA signature (miR-Score) that was able to predict an OS of ≥20 months. Performance of the miR-Score was evaluated by receiver operating characteristic (ROC) curve analysis and validated in a series of 43 tumor samples from patients who underwent palliative surgery [pleurectomy/decortication (P/D)].
  
  
  RESULTS
  The miR-Score, using expression data of six microRNAs (miR-21-5p, -23a-3p, -30e-5p, -221-3p, -222-3p, and -31-5p), enabled prediction of long survival with an accuracy of 92.3% for EPP and 71.9% for palliative P/D. Hazard ratios for score-negative patients were 4.12 (95% CI: 2.03-8.37) for EPP and 1.93 (95% CI: 1.01-3.69) for P/D. Importantly, adding the miR-Score to a set of clinical selection criteria (histology, age, gender) increased predictive accuracy in the independent validation set from 76.3% for clinical factors only to 87.3%.
  
  
  CONCLUSIONS
  This study has identified a novel 6-microRNA signature (miR-Score) that can accurately predict prognosis of MPM patients.
authors.affiliation: Asbestos Diseases Research Institute (ADRI), Sydney, NSW, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW, Australia. Electronic address: michaela.kirschner@sydney.edu.au.
authors.forename: Michaela B
authors.initials: MB
authors.lastname: Kirschner
authors.affiliation: Asbestos Diseases Research Institute (ADRI), Sydney, NSW, Australia. Electronic address: yuen.cheng@sydney.edu.au.
authors.forename: Yuen Yee
authors.initials: YY
authors.lastname: Cheng
authors.affiliation: School of Mathematics and Statistics, The University of Sydney, Sydney, NSW, Australia. Electronic address: nicola.armstrong@sydney.edu.au.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Armstrong
authors.affiliation: Asbestos Diseases Research Institute (ADRI), Sydney, NSW, Australia; School of Biotechnology and Biomolecular Sciences, University of New South Wales, NSW, Australia. Electronic address: ruby.lin@sydney.edu.au.
authors.forename: Ruby C Y
authors.initials: RC
authors.lastname: Lin
authors.affiliation: Asbestos Diseases Research Institute (ADRI), Sydney, NSW, Australia; Department of Medical Oncology, Chris O'Brien Lifehouse, Sydney, NSW, Australia. Electronic address: Steven.Kao@lh.org.au.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Kao
authors.affiliation: Asbestos Diseases Research Institute (ADRI), Sydney, NSW, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Concord Repatriation General Hospital, Sydney, NSW, Australia. Electronic address: anthony.linton@sydney.ed.au.
authors.forename: Anthony
authors.initials: A
authors.lastname: Linton
authors.affiliation: Department of Anatomical Pathology, Flinders Medical Centre, Adelaide, SA, Australia. Electronic address: Sonja.Klebe@health.sa.gov.au.
authors.forename: Sonja
authors.initials: S
authors.lastname: Klebe
authors.affiliation: Sydney Cardiothoracic Surgeons, RPA Medical Centre, Sydney, NSW, Australia. Electronic address: brianmccaughan@gmail.com.
authors.forename: Brian C
authors.initials: BC
authors.lastname: McCaughan
authors.affiliation: Asbestos Diseases Research Institute (ADRI), Sydney, NSW, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW, Australia. Electronic address: nico.vanzandwijk@sydney.edu.au.
authors.forename: Nico
authors.initials: N
authors.lastname: van Zandwijk
authors.affiliation: Asbestos Diseases Research Institute (ADRI), Sydney, NSW, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW, Australia. Electronic address: glen.reid@sydney.edu.au.
authors.forename: Glen
authors.initials: G
authors.lastname: Reid
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D008654:Mesothelioma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000086002:Mesothelioma, Malignant; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D010166:Palliative Care; D011013:Pneumonectomy; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D035683:MicroRNAs
keywords: Biomarker; Malignant pleural mesothelioma; MicroRNAs; Prognosis; Survival