title: Circulating miRNA95 and miRNA190 are sensitive markers for the differential diagnosis of thyroid nodules in a Caucasian population.
abstract: BACKGROUND
  MicroRNA (miRNAs) are nonprotein-encoding RNAs that regulate gene expression and enable the distinction of benign from malignant tissues in human cancers.
  
  
  OBJECTIVE
  We investigated the role of miRNA circulating in the blood for the differential diagnosis of thyroid nodules.
  
  
  METHODS
  miRNA profiling was assessed by TaqMan Array Human MicroRNA A Cards 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 down-regulated, and miR190, -362-3p, -518a-5p up-regulated) which differ in PTC compared with NG and HS. 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
  We have identified for the first time two miRNAs differently 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."
authors: Department of Medicine, Surgery and Neuroscience (S.Can., T.P., G.S., G.B., S.Car., F.D., F.P.), University of Siena, Siena, Italy; Fondazione Umberto Di Mario ONLUS (G.S., F.D.), Toscana Life Sciences, Siena, Italy; and Department of Medical Biotechnologies (G.C.), University of Siena, Siena, Italy.
authors: Silvia
authors: S
authors: Cantara
authors: Tania
authors: T
authors: Pilli
authors: Guido
authors: G
authors: Sebastiani
authors: Gabriele
authors: G
authors: Cevenini
authors: Giulia
authors: G
authors: Busonero
authors: Sandro
authors: S
authors: Cardinale
authors: Francesco
authors: F
authors: Dotta
authors: Furio
authors: F
authors: Pacini
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002291:Carcinoma, Papillary / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D006044:Goiter, Nodular / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D012680:Sensitivity and Specificity; D013964:Thyroid Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D016606:Thyroid Nodule / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D044465:White People; D055815:Young Adult
chemical_list: D015415:Biomarkers; C576613:MIRN190 microRNA, human; C575854:MIRN95 microRNA, human; D035683:MicroRNAs