MECHANISMS IN ENDOCRINOLOGY: MicroRNA in diagnostics and therapy of thyroid cancer

Abstract

MicroRNAs, short non-coding regulators of the gene expression, are subjects of numerous investigations assessing their potential use in the diagnostics and management of human diseases. In this review, we focus on studies that analyze the utility of microRNAs as novel diagnostic and therapeutic tools in follicular cell-derived thyroid carcinomas. This very interesting and promising field brings new insight into future strategies for personalized medicine.

New molecular biomarkers in differentiated thyroid carcinoma: Impact of miR‐146, miR‐221 and miR‐222 levels in the evolution of the disease

“…Therefore, it was shown that miR‐146 expression levels in tumour tissue have a prognostic value in patients with papillary carcinoma and that may be used as a significant predictor of the evolution of disease associated with tumour stage and extrathyroid invasion at the time of surgery . Similar results have been found in other studies for the miR‐221 and miR‐222 families, which are higher in tumours with worse prognostic characteristics such as increased tumour size, capsular, vascular or lymphatic invasion or presence of metastases . Those findings are consistent with our observations.…”

“…These results highlight the importance of miR‐146b as a determinant of the aggressiveness of papillary carcinoma and the identification of target genes potentially related to tumour aggressiveness . Similar results have been found in other studies for the miR‐221 and miR‐222 families, with higher levels in tumours with worse prognostic characteristics …”

“…The study of circulating microRNAs is much more recent in this field, and there are still few data. Yu et al demonstrated the presence of miR‐222, whose levels were higher in the peripheral blood of patients with papillary carcinoma compared to patients with benign nodules . Lee et al carried out a similar analysis, finding that miR‐222 and miR‐146 were overexpressed in patients with recurrent papillary carcinoma compared to those who had not recurred and could be detected in plasma from patients with papillary carcinoma at levels much higher than in healthy patients …”

Association of microRNA-related gene XPO5 rs11077 polymorphism with susceptibility to thyroid cancer

“…[3–5] With the development of epigenetics, microRNAs (miRNAs) have been discovered to participate in the occurrence and development of TC, which also interact with the alteration of environmental factors. [6,7] …”

Presencia de la mutación BRAFV600E en nódulos tiroideos, y su relación con el diagnóstico citológico y anatomopatológico de carcinoma de tiroides

“….5.3 Otros marcadoresLos microRNA (miRNA) y su expresión se han estudiado en carcinoma papilar de tiroides, encontrándose que miR-221, miR-222 y miR-146b, entre otros, se expresan al alta en este tipo de cáncer, y se correlacionan con el estado mutacional del carcinoma papilar68 .Se ha atribuido el polimorfismo rs2910464G>C en el miR-146a-3p a un alto riesgo de desarrollo de carcinoma papilar familiar en pacientes caucásicos siendo protector el polimorfismo C>C, si bien otros estudios son controversiales73 .En estudios de expresión de miRNA en muestras de ACAF se han encontrado valores de exactitud entre 37% y 90%, con sensibilidad entre 79% y 100% y especificidad entre 20% y 95%73,74 . Se considera que se requieren más estudios para determinar su utilidad.Se ha empleado además la tecnología Next Generation Sequencing mediante una plataforma (ThyroSeq) que permite detectar una serie de 12 genes con 284 puntos hotspot, que incluyen BRAF, RAS y los rearreglos RET/PTC y PAX8/PPARG, además de otros genes asociados a carcinoma papilar de tiroides pero de menor frecuencia.…”