MicroRNA profile of poorly differentiated thyroid carcinomas: new diagnostic and prognostic insights

Abstract

The diagnosis of conventional and oncocytic poorly differentiated thyroid carcinomas is difficult. The aim of this study was to characterize their largely unknown miRNA expression profile and to compare it to well differentiated thyroid tumors as well as to identify miRNAs which could potentially serve as diagnostic and prognostic markers. A total of 14 poorly differentiated, 13 oncocytic poorly differentiated, 72 well differentiated thyroid carcinomas and 8 normal thyroid specimens were studied for expression of 768 miRNAs using PCR-Microarrays. MiRNA expression was different between poorly differentiated and oncocytic poorly differentiated thyroid carcinomas demonstrating individual clusters on the clustering analysis. Both tumor types showed upregulation of miR-125a-5p, -15a-3p, -182, -183-3p, -222, -222-5p and downregulation of miR-130b, -139-5p, -150, -193a-5p, -219-5p, -23b, -451, -455-3p and of miR-886-3p as compared to normal thyroid tissue. In addition, the oncocytic poorly differentiated thyroid carcinomas demonstrated upregulation of miR-221 and miR-885-5p. The difference in expression was also observed between miRNA expression in poorly differentiated and well differentiated tumors. The CHAID algorithm allowed to separate poorly differentiated from well differentiated thyroid carcinomas with a 73–79% accuracy using miR-23b and miR-150 as a separator. Kaplan-Meier and multivariate analysis showed a significant association with tumor relapses (for miR-23b) and with tumor specific death (for miR-150) in poorly differentiated and oncocytic poorly differentiated thyroid carcinomas. MiRNA expression is different in conventional and oncocytic poorly differentiated thyroid carcinomas in comparison to well differentiated thyroid cancers and can be used for discrimination between these tumor types. The newly identified deregulated miRNAs (miR-150, miR-23b) bear the potential to be used in a clinical setting delivering prognostic and diagnostic information.

MicroRNA deep-sequencing reveals master regulators of follicular and papillary thyroid tumors

“…34 Further, miR-150 was downregulated specifically in follicular carcinomas. In line with its recently described downregulation in poorly differentiated thyroid tumors, 35 the candidate targets identified here (FGF12, PRKCA, and TGFBR1) could lead to a more aggressive neoplasm.…”

miR-130b-3p Upregulation Contributes to the Development of Thyroid Adenomas Targeting <b><i>CCDC6</i></b> Gene

“…5). Notably, downregulation of miR-130b expression was recently reported in thyroid carcinomas [18]. The confirmation of these results in a very large number of FTAs and follicular thyroid carcinomas, and hopefully in fine-needle thyroid biopsies from these neoplasias, might open the perspective of the detection of miR-130b-3p as a useful marker for the differential diagnosis between FTA and follicular thyroid carcinoma, which still represents the main challenge in thyroid pathology.…”

Pathobiology of MicroRNAs and Their Emerging Role in Thyroid Fine-Needle Aspiration

“…In this instance, miR-885-5p possibly plays a role in oncocytic tumor mitochondria accumulation. In addition, poorly differentiated oncocytic carcinomas show miR-221 and miR-885-5p upregulation [37,39,40]. …”

“…Poorly differentiated carcinomas can be separated from well-differentiated carcinomas with 73-79% accuracy by miR-23b and miR-150, with both of these miRs having prognostic potential [40]. The pathobiology of anaplastic thyroid cancer (ATC) is associated with the downregulation of many miRs in contrast to other thyroid carcinomas of follicular cell origin [29].…”