MicroRNA signatures in malignant pleural mesothelioma effusions

Abstract

Introduction/Aim Malignant pleural mesothelioma (MPM) is an incurable cancer of the pleura that can be difficult to diagnose. Biomarkers for an earlier and/or easier diagnosis are urgently needed. The powerful gene regulators microRNA, have become popular diagnostic targets due to their stable expression within the body. Studies have examined microRNA in MPM and control samples, however it is still unclear which microRNA are potential biomarkers for MPM. Approximately 90% of patients develop pleural effusions which are an ideal source of diagnostic targets as sample collection is minimally invasive. The biomarker potential of microRNA in MPM frozen/fresh effusions is yet to be determined. We hypothesise that microRNA expressed in effusions are potential biomarkers for MPM. Methods Taqman OpenArray profiling and real-time quantitative PCR were used to analyse microRNA in a cohort (Cohort 1) of 48 effusion cell and supernatant samples from MPM, lung adenocarcinoma and benign pleural disease patients. The potential microRNA biomarkers were then analysed in a second cohort (Cohort 2) of 60 MPM and lung adenocarcinoma samples. Statistics MicroRNA expression was determined to be significantly different between diseases on a volcano plot with a 2 or more-fold change and a p< 0.05. MicroRNA combinations were analysed using logistic regression and diagnostic efficiency was assessed using receiver operating characteristic curves. Results An effusion cell signature based on the combination of miR-143, miR-210 and miR-200c for the diagnosis of MPM was identified in Cohort 1 (AUC – 0.92) and validated in Cohort 2 (AUC – 0.71). Conclusion MicroRNA expressed in effusion cells are potential biomarkers for differentiating MPM from lung adenocarcinoma. Grant Support: This work was supported by grants from Dust Diseases Board N.S.W, Maurice Blackburn and Sir Charles Gairdner Hospital Research Committee. S Mutsaers was supported on a Cancer Council WA Research Fellowship