Analysis of circulating extracellular vesicle-associated microRNAs in cortisol-producing adrenocortical tumors

Perge, Pál and Decmann, Ábel and Pezzani, R. and Bancos, I. and Fassina, A. and Tóth, Miklós and Patócs, Attila Balázs and Igaz, Péter (2018) Analysis of circulating extracellular vesicle-associated microRNAs in cortisol-producing adrenocortical tumors. ENDOCRINE, 59 (2). pp. 280-287. ISSN 1355-008X

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Abstract

PURPOSE: Circulating microRNAs (miRNA) have been described in patients with adrenocortical tumors, but the expression of miRNAs in non-functioning and cortisol-producing tumors has not been yet compared. Therefore, the objective of this study was to evaluate the expression of plasma extracellular vesicle (EV)-associated microRNAs in patients with non-functioning adrenocortical adenoma (NFA), cortisol-producing adrenocortical adenoma (CPA) and cortisol-producing adrenocortical carcinoma (CP-ACC). METHODS: Preoperative plasma EV samples of 13 NFAs, 13 CPAs and 9 CP-ACCs were subjected to extracellular vesicle isolation. miRNAs were investigated by targeted quantitative real-time PCR normalized to cel-miR-39 as reference. Five miRNAs have been selected for this analysis based on the previous studies including hsa-miR-22-3p, hsa-miR-27a-3p, hsa-miR-210-3p, hsa-miR-320b and hsa-miR-375. RESULTS: We have observed significant overrepresentation of three miRNAs in both CPA and CP-ACC relative to NFA: hsa-miR-22-3p (p < 0.01 and p < 0.0001, respectively), hsa-miR-27a-3p (p < 0.05 in both comparisons) and hsa-miR-320b (p < 0.05 and p < 0.0001, respectively). Hsa-miR-320b has been significantly overrepresented in CP-ACC relative to CPA (p < 0.01). Hsa-miR-210-3p turned out to be significantly overrepresented only in CP-ACC compared to NFA (p < 0.05). Significant correlation was revealed between circulating miRNA concentrations and urinary free cortisol values for hsa-miR-22-3p, hsa-miR-27a-3p and hsa-miR-320b (p < 0.0001 for all) and cortisol after low-dose dexamethasone test for hsa-miR-22-3p and hsa-miR-320b (p < 0.05). Hsa-miR-27a-3p has been significantly stimulated by low-dose dexamethasone test (p < 0.05). CONCLUSIONS: EV-associated miRNAs are differentially expressed in different non-functioning and cortisol-producing adrenocortical tumors.

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