Multicentric characterization and validation of a molecular diagnostic test for the classification of indeterminate thyroid nodules based on microRNA profiling

Abstract

Thyroid nodules may be found by palpation in 1 to 7% of the population. Brazilian and international guidelines recommend that nodes greater than 1 cm in patients with normal thyroid function, should be drained through Fine Needle Aspiration (FNA). About 65 to 80% of punctured nodules are considered benign and 5 to 15% malignant. However, between 15 and 30% are classified as indeterminate and they are directed to surgical thyroidectomy, but postsurgical final histological analysis reclassifies 70 to 80 % of the cases as benign, showing the high rate of unnecessary surgeries. Several molecular techniques have been developed trying to help to solve this problem. Besides the high costs, none of these tests is made in Brazil and some techniques have limited specificity and sensitivity, limiting their usage for directing the clinical conduct. At the project developed with FAPESP grant for PIPE Fase 1, in a partnership with the Cancer Hospital of Barretos and the Swiss startup SimplicityBio, ONKOS developed the mir-THYpe®, a new test for classification of indeterminate thyroid nodules. Through the analysis of molecular signatures generated by the expression profile of 12 microRNAs (microRNA profiling), mir-THYpe® showed 95% sensibility, 71% specificity, 91% of negative predictive value (NPV), 82% of positive predictive value, with 85% accuracy, highlighting its potential to help the clinical management of patients and its efficiency and competitiveness when compared to other commercially available tests. However, it was initially validated with a group of only 67 samples and now a bigger and more diverse cohort is necessary to generate more robust data that will evidence its efficiency. Thus, the aim of this project is to do a multicenter validation of mir-THYpe® and the optimization of the algorithm through different analysis strategies and data modeling. About 48,000 surgeries are performed unnecessarily each year in Brazil and generate an expense of R$ 135 million, so the potential clinical impact in reducing this number of unnecessary surgeries and the amount that the health system can save, besides having more affordable price than competitors, once it is a national technology, are factors that contribute to the success of this product. (AU)