Circulating miRNA95 and miRNA190 are sensitive markers for the differential diagnosis of thyroid nodules in a Caucasian population

Abstract

Context: MicroRNA (miRNAs) are nonprotein-encoding RNAs that regulate gene expression and enable the distinction of benign from malignant tissues in human cancers. Objective: Weinvestigated the role of miRNA circulating in the blood for the differential diagnosis of thyroid nodules. Setting and Design: miRNA profiling was assessed by TaqMan ArrayHumanMicroRNAACards v2.0 in pooled sera from 12 healthy subjects (HS), 12 nodular goiters (NG), and 12 patients with papillary thyroid cancer (PTC) (cohort 1). From this analysis, we selected eight miRNAs that were validated in individual samples (same of cohort 1) by qRT-PCR. Four miRNAs were confirmed differentially expressed in PTC and were analyzed in a larger second cohort. Results: The profiling analysis revealed eight miRNAs (miRNA579,-95,-29b, 5-01-3p,-548d-5p downregulated, andmiR190,-362-3p,-518a-5p up-regulated) which differ inPTCcomparedwithNGandHS. After the validation in individual samples, we confirmed as differentially expressed miRNA579,-95,-29b, and miRNA190. These miRNAs were further validated in a second cohort of sera from 79 PTC, 80 NG, and 41 HS. MiRNA95 had a sensitivity of 94.9%, which reached 100% in a multivariate risk model combined with miRNA190. We developed a mathematical formula that calculates the probability of malignancy with a cut-off value of 0.5 above which the patient was at high risk of malignancy. Conclusions: Wehave identified for the first timetwomiRNAsdifferently expressed in serum of PTC patients who in combination allow the differential diagnosis of thyroid nodules with great accuracy in our study population. Additional studies are required; however, to define whether these results will also be generalized across other patient populations.