title: MicroRNA-based molecular classification of papillary thyroid carcinoma.
abstract: MicroRNA (miRNA) expression is dysregulated in many human malignancies, and a growing number of studies are focused on their potential use as tumor biomarkers. To identify a miRNA signature for papillary thyroid carcinomas (PTC), we investigated miRNA expression profiles in two independent cohorts of PTCs, which included major histological subtypes [classical-type (PTC‑CT), follicular-variant (PTC‑FV), and tall-cell variant (PTC‑TCV)] and cases with low or intermediate risk of recurrence. Using TaqMan® Array Human MicroRNA A+B Cards v3.0, we first performed microRNA profiling of normal and neoplastic thyroid tissues from 29 PTC patients. Promising candidates were then investigated in a second, independent cohort of 76 PTCs using Custom TaqMan® Array MicroRNA Cards. We identified a molecular signature of 11 miRNAs that were significantly upregulated (miR‑146b-5p, miR‑146b-3p, miR‑221-3p, miR‑222‑5p, miR‑222‑3p) or downregulated (miR‑1179, miR‑486‑5p, miR‑204-5p, miR‑7-2-3p, miR‑144-5p, miR‑140-3p) in PTC tissues vs. normal thyroid tissue. Upregulation of miR‑146b-5p and miR‑222‑3p was also significantly associated with an increased risk of recurrence. Higher than normal expression of miR‑146b-5p and miR‑146b-3p characterized PTC‑CT and PTC‑TCV but not PTC‑FV, whereas miR‑21-5p was significantly upregulated only in PTC‑TCV. When PTC‑FV were subclassified as encapsulated (PTC‑EFV) or infiltrative (PTC‑IFV), miR‑204-5p was downregulated in all histological subtypes except PTC‑EFV, which displayed expression levels similar to those of normal thyroid tissues. These findings provide new insights into the molecular classification of PTC, showing that different miRNA expression profiles are associated with different histological types of PTC and different risks of recurrence.
authors.affiliation: Department of Internal Medicine and Medical Specialties, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Rosignolo
authors.affiliation: Department of Experimental Oncology, Mediterranean Institute of Oncology, Viagrande, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Memeo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Monzani
authors.affiliation: Department of Experimental Oncology, Mediterranean Institute of Oncology, Viagrande, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Colarossi
authors.affiliation: Department of Internal Medicine and Medical Specialties, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Pecce
authors.affiliation: Department of Internal Medicine and Medical Specialties, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Verrienti
authors.affiliation: Department of Internal Medicine and Medical Specialties, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Cosimo
authors.initials: C
authors.lastname: Durante
authors.affiliation: Department of Internal Medicine and Medical Specialties, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Grani
authors.affiliation: Department of Internal Medicine and Medical Specialties, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Livia
authors.initials: L
authors.lastname: Lamartina
authors.affiliation: IOM Ricerca, Viagrande, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Forte
authors.affiliation: IOM Ricerca, Viagrande, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Martinetti
authors.affiliation: Department of Experimental Oncology, Mediterranean Institute of Oncology, Viagrande, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Giuffrida
authors.affiliation: Department of Health Sciences, University of Catanzaro 'Magna Graecia', Catanzaro, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Russo
authors.affiliation: Department of Histopathology, University of Pisa, Pisa, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Basolo
authors.affiliation: Department of Internal Medicine and Medical Specialties, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Filetti
authors.affiliation: Department of Internal Medicine and Medical Specialties, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Sponziello
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002277:Carcinoma / Q000145:classification / Q000235:genetics* / Q000473:pathology; D002291:Carcinoma, Papillary; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics; D008875:Middle Aged; D011379:Prognosis; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000473:pathology; D013964:Thyroid Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs