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MiR-Score: A novel 6-microRNA signature that predicts survival outcomes in patients with malignant pleural mesothelioma

Kirschner, M.B., Cheng, Y.Y., Armstrong, N.J., Lin, R.C.Y., Kao, S.C., Linton, A., Klebe, S., McCaughan, B.C., van Zandwijk, N. and Reid, G. (2015) MiR-Score: A novel 6-microRNA signature that predicts survival outcomes in patients with malignant pleural mesothelioma. Molecular Oncology, 9 (3). pp. 715-726.

Link to Published Version: http://dx.doi.org/10.1016/j.molonc.2014.11.007
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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.

Publication Type: Journal Article
Publisher: Elsevier Ltd.
Copyright: © 2014 Federation of European Biochemical Societies
URI: http://researchrepository.murdoch.edu.au/id/eprint/29606
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