New molecular biomarkers in differentiated thyroid carcinoma: Impact of miR-146, miR-221 and miR-222 levels in the evolution of the disease

Objective MircroRNAs (miR) are small, noncoding RNA molecules of 18-25 nucleotides. Their dysregulation has been widely studied in many human tumours including differentiated thyroid cancer (DTC). miRs more frequently associated with these kinds of tumours are miR-146, miR-221 and miR-222. Our objective was to assess the relationship among circulating miR levels and the evolution and outcomes of disease. Design We analysed a sample of 60 patients with DTC assigning them to one of three groups according to the dynamic scale of risk (excellent response, incomplete biochemical response and incomplete structural response). Patients and measurements At study inclusion, we determined thyroid-stimulating hormone, thyroxine, thyroglobulin, antithyroglobulin antibodies and plasma levels of miR-146, miR-221 and miR-222. Results Male sex and advanced age at diagnosis were associated with the worst disease progression. miR-222 was twofold to threefold higher in tall cell papillary carcinomas (P = 0.038). miR-146 (P = 0.016) and miR-221 (P = 0.050) had a positive correlation with thyroglobulin at the time of sampling. In regression analysis, miR-146 (P = 0.006), miR-221 (P = 0.004) and miR-222 (P = 0.007) predicted more than 70% of the variation in thyroglobulin levels at the time of sampling. Conclusions Elevated miR-222 and miR-146 levels are associated with poorer outcomes of the disease and may have a prognostic value in the management and follow-up of DTC.