Diagnostic and Prognostic Value of microRNAs for Environmental Exposure to Asbestiform Fibers Causing the Malignant Mesothelioma

Abstract BackgroundFluoro-edenite (FE) is an asbestiform fiber identified in the lavic products of Monte Calvario from stone quarries located in the southeast of Biancavilla (Sicily, Italy). Environmental exposure to this silicate has been associated with a higher incidence of Malignant Mesothelioma (MM), highly aggressive cancer that affects the pleural tissue. Median survival for MM was 9.8 months, with 5% of patients surviving at 5 years. At present, several diagnostic biomarkers have been evaluated for MM and many studies demonstrated that microRNAs (miRNAs) have the potential to be considered as good non-invasive diagnostic and prognostic biomarkers for cancer.A set of miRNAs involved in MM was previously identified after a careful in silico selection. Starting from these preliminary data, this study aimed to validate the predicted diagnostic significance of hsa-miR-323a-3p, hsa-miR-101-3p, and hsa-miR-20b-5p on a subset of MM patients exposed to FE and matched healthy controls. For this purpose, MM tissues vs. nonmalignant pleura tissues were analyzed through droplet digital PCR to evaluate differences in the expression levels of these miRNAs and their MM diagnostic potential. In addition, computational analysis have been performed to establish the correlation of these miRNAs with the online available asbestos exposure data and clinic-pathological parameters to verify a potential role of these miRNAs as prognostic tools. The interaction between these miRNAs and the main genes mutated and altered in MM was evaluated.ResultsDroplet digital PCR results showed that the three analyzed miRNAs were significantly down-regulated in MM cases vs. controls. ROC analysis revealed high specificity and sensitivity rates for both hsa-miR-323a-3p, and hsa-miR-20b-5p, which thus acquire a diagnostic value for MM. In silico results showed a potential prognostic role of hsa-miR-101-3p due to a significant association of its higher expression and increased Overall Survivor of MM patients. Finally, the computational analysis have showed that these miRNAs can target and modulate both oncogene and tumor suppressor genes.ConclusionsThese miRNAs should be further evaluated not only as diagnostic tools, but also as prognostic predictors. Furthermore, the validation of their targets and regulators would clarify how miRNAs induce or repress critical pathways involved in the carcinogenesis triggered by carcinogenic fibers exposure.