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

Pál Perge, Ábel Decmann, Raffaele Pezzani, Irina Bancos, Ambrogio Fassina, Michaela Luconi, Letizia Canu, Miklós Tóth, Marco Boscaro, A. Patócs, P. Igaz

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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.

Original languageEnglish
Pages (from-to)280-287
Number of pages8
JournalEndocrine
Volume59
Issue number2
DOIs
Publication statusPublished - Feb 1 2018

Fingerprint

MicroRNAs
Hydrocortisone
Adrenocortical Adenoma
Adrenocortical Carcinoma
Neoplasms
Dexamethasone
Extracellular Vesicles
Real-Time Polymerase Chain Reaction
human MIRN22 microRNA

Keywords

  • Adenoma
  • Adrenocortical
  • Carcinoma
  • Cortisol
  • Extracellular vesicle
  • MicroRNA

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Analysis of circulating extracellular vesicle-associated microRNAs in cortisol-producing adrenocortical tumors. / Perge, Pál; Decmann, Ábel; Pezzani, Raffaele; Bancos, Irina; Fassina, Ambrogio; Luconi, Michaela; Canu, Letizia; Tóth, Miklós; Boscaro, Marco; Patócs, A.; Igaz, P.

In: Endocrine, Vol. 59, No. 2, 01.02.2018, p. 280-287.

Research output: Contribution to journalArticle

Perge, P, Decmann, Á, Pezzani, R, Bancos, I, Fassina, A, Luconi, M, Canu, L, Tóth, M, Boscaro, M, Patócs, A & Igaz, P 2018, 'Analysis of circulating extracellular vesicle-associated microRNAs in cortisol-producing adrenocortical tumors', Endocrine, vol. 59, no. 2, pp. 280-287. https://doi.org/10.1007/s12020-017-1506-z
Perge, Pál ; Decmann, Ábel ; Pezzani, Raffaele ; Bancos, Irina ; Fassina, Ambrogio ; Luconi, Michaela ; Canu, Letizia ; Tóth, Miklós ; Boscaro, Marco ; Patócs, A. ; Igaz, P. / Analysis of circulating extracellular vesicle-associated microRNAs in cortisol-producing adrenocortical tumors. In: Endocrine. 2018 ; Vol. 59, No. 2. pp. 280-287.
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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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AU - Perge, Pál

AU - Decmann, Ábel

AU - Pezzani, Raffaele

AU - Bancos, Irina

AU - Fassina, Ambrogio

AU - Luconi, Michaela

AU - Canu, Letizia

AU - Tóth, Miklós

AU - Boscaro, Marco

AU - Patócs, A.

AU - Igaz, P.

PY - 2018/2/1

Y1 - 2018/2/1

N2 - 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.

AB - 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.

KW - Adenoma

KW - Adrenocortical

KW - Carcinoma

KW - Cortisol

KW - Extracellular vesicle

KW - MicroRNA

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