Michaela B Kirschner1, Yuen Yee Cheng2, Nicola J Armstrong3, Ruby C Y Lin4, Steven C Kao5, Anthony Linton6, Sonja Klebe7, Brian C McCaughan8, Nico van Zandwijk9, Glen Reid10. 1. 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. 2. Asbestos Diseases Research Institute (ADRI), Sydney, NSW, Australia. Electronic address: yuen.cheng@sydney.edu.au. 3. School of Mathematics and Statistics, The University of Sydney, Sydney, NSW, Australia. Electronic address: nicola.armstrong@sydney.edu.au. 4. 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. 5. 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. 6. 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. 7. Department of Anatomical Pathology, Flinders Medical Centre, Adelaide, SA, Australia. Electronic address: Sonja.Klebe@health.sa.gov.au. 8. Sydney Cardiothoracic Surgeons, RPA Medical Centre, Sydney, NSW, Australia. Electronic address: brianmccaughan@gmail.com. 9. 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. 10. 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.
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.
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: Steven Chuan-Hao Kao; Sonja Klebe; Douglas W Henderson; Glen Reid; Mark Chatfield; Nicola J Armstrong; Tristan D Yan; Janette Vardy; Stephen Clarke; Nico van Zandwijk; Brian McCaughan Journal: J Thorac Oncol Date: 2011-11 Impact factor: 15.609
Authors: Burkhard Kneitz; Markus Krebs; Charis Kalogirou; Maria Schubert; Steven Joniau; Hein van Poppel; Evelyne Lerut; Susanne Kneitz; Claus Jürgen Scholz; Philipp Ströbel; Manfred Gessler; Hubertus Riedmiller; Martin Spahn Journal: Cancer Res Date: 2014-03-07 Impact factor: 12.701
Authors: Nico van Zandwijk; Christopher Clarke; Douglas Henderson; A William Musk; Kwun Fong; Anna Nowak; Robert Loneragan; Brian McCaughan; Michael Boyer; Malcolm Feigen; David Currow; Penelope Schofield; Beth Ivimey Nick Pavlakis; Jocelyn McLean; Henry Marshall; Steven Leong; Victoria Keena; Andrew Penman Journal: J Thorac Dis Date: 2013-12 Impact factor: 2.895
Authors: S Cedrés; M A Montero; P Martinez; A Martinez; V Rodríguez-Freixinós; D Torrejon; A Gabaldon; M Salcedo; S Ramon Y Cajal; E Felip Journal: Lung Cancer Date: 2012-03-27 Impact factor: 5.705
Authors: Mohamed Guled; Leo Lahti; Pamela M Lindholm; Kaisa Salmenkivi; Izhar Bagwan; Andrew G Nicholson; Sakari Knuutila Journal: Genes Chromosomes Cancer Date: 2009-07 Impact factor: 5.006
Authors: A Linton; Y Y Cheng; K Griggs; Lyn Schedlich; M B Kirschner; S Gattani; S Srikaran; S Chuan-Hao Kao; B C McCaughan; S Klebe; N van Zandwijk; G Reid Journal: Br J Cancer Date: 2013-12-10 Impact factor: 7.640
Authors: Fabian Dominik Mairinger; Robert Werner; Elena Flom; Jan Schmeller; Sabrina Borchert; Michael Wessolly; Jeremias Wohlschlaeger; Thomas Hager; Thomas Mairinger; Jens Kollmeier; Daniel Christian Christoph; Kurt Werner Schmid; Robert Fred Henry Walter Journal: Virchows Arch Date: 2017-05-02 Impact factor: 4.064