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Circulating microRNA Expression in Cushing’s Syndrome

CONTEXT: Cushing’s syndrome (CS) is a rare disease of endogenous hypercortisolism associated with high morbidity and mortality. Diagnosis and classification of CS is still challenging. OBJECTIVE: Circulating microRNAs (miRNAs) are minimally invasive diagnostic markers. Our aim was to characterize th...

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Autores principales: Vetrivel, Sharmilee, Zhang, Ru, Engel, Mareen, Altieri, Barbara, Braun, Leah, Osswald, Andrea, Bidlingmaier, Martin, Fassnacht, Martin, Beuschlein, Felix, Reincke, Martin, Chen, Alon, Sbiera, Silviu, Riester, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937959/
https://www.ncbi.nlm.nih.gov/pubmed/33692756
http://dx.doi.org/10.3389/fendo.2021.620012
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author Vetrivel, Sharmilee
Zhang, Ru
Engel, Mareen
Altieri, Barbara
Braun, Leah
Osswald, Andrea
Bidlingmaier, Martin
Fassnacht, Martin
Beuschlein, Felix
Reincke, Martin
Chen, Alon
Sbiera, Silviu
Riester, Anna
author_facet Vetrivel, Sharmilee
Zhang, Ru
Engel, Mareen
Altieri, Barbara
Braun, Leah
Osswald, Andrea
Bidlingmaier, Martin
Fassnacht, Martin
Beuschlein, Felix
Reincke, Martin
Chen, Alon
Sbiera, Silviu
Riester, Anna
author_sort Vetrivel, Sharmilee
collection PubMed
description CONTEXT: Cushing’s syndrome (CS) is a rare disease of endogenous hypercortisolism associated with high morbidity and mortality. Diagnosis and classification of CS is still challenging. OBJECTIVE: Circulating microRNAs (miRNAs) are minimally invasive diagnostic markers. Our aim was to characterize the circulating miRNA profiles of CS patients and to identify distinct profiles between the two major CS subtypes. METHODS: We included three groups of patients from the German Cushing’s registry: ACTH-independent CS (Cortisol-Producing-Adenoma; CPA), ACTH-dependent pituitary CS (Cushing’s Disease; CD), and patients in whom CS had been ruled out (controls). Profiling of miRNAs was performed by next-generation-sequencing (NGS) in serum samples of 15 CS patients (each before and after curative surgery) and 10 controls. Significant miRNAs were first validated by qPCR in the discovery cohort and then in an independent validation cohort of 20 CS patients and 11 controls. RESULTS: NGS identified 411 circulating miRNAs. Differential expression of 14 miRNAs were found in the pre- and postoperative groups. qPCR in the discovery cohort validated 5 of the significant miRNAs from the preoperative group analyses. Only, miR-182-5p was found to be significantly upregulated in the CD group of the validation cohort. Comparing all CS samples as a group with the controls did not reveal any significant differences in expression. OUTCOME: In conclusion, our study identified miR-182-5p as a possible biomarker for CD, which has to be validated in a prospective cohort. Furthermore, our results suggest that presence or absence of ACTH might be at least as relevant for miRNA expression as hypercortisolism itself.
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spelling pubmed-79379592021-03-09 Circulating microRNA Expression in Cushing’s Syndrome Vetrivel, Sharmilee Zhang, Ru Engel, Mareen Altieri, Barbara Braun, Leah Osswald, Andrea Bidlingmaier, Martin Fassnacht, Martin Beuschlein, Felix Reincke, Martin Chen, Alon Sbiera, Silviu Riester, Anna Front Endocrinol (Lausanne) Endocrinology CONTEXT: Cushing’s syndrome (CS) is a rare disease of endogenous hypercortisolism associated with high morbidity and mortality. Diagnosis and classification of CS is still challenging. OBJECTIVE: Circulating microRNAs (miRNAs) are minimally invasive diagnostic markers. Our aim was to characterize the circulating miRNA profiles of CS patients and to identify distinct profiles between the two major CS subtypes. METHODS: We included three groups of patients from the German Cushing’s registry: ACTH-independent CS (Cortisol-Producing-Adenoma; CPA), ACTH-dependent pituitary CS (Cushing’s Disease; CD), and patients in whom CS had been ruled out (controls). Profiling of miRNAs was performed by next-generation-sequencing (NGS) in serum samples of 15 CS patients (each before and after curative surgery) and 10 controls. Significant miRNAs were first validated by qPCR in the discovery cohort and then in an independent validation cohort of 20 CS patients and 11 controls. RESULTS: NGS identified 411 circulating miRNAs. Differential expression of 14 miRNAs were found in the pre- and postoperative groups. qPCR in the discovery cohort validated 5 of the significant miRNAs from the preoperative group analyses. Only, miR-182-5p was found to be significantly upregulated in the CD group of the validation cohort. Comparing all CS samples as a group with the controls did not reveal any significant differences in expression. OUTCOME: In conclusion, our study identified miR-182-5p as a possible biomarker for CD, which has to be validated in a prospective cohort. Furthermore, our results suggest that presence or absence of ACTH might be at least as relevant for miRNA expression as hypercortisolism itself. Frontiers Media S.A. 2021-02-22 /pmc/articles/PMC7937959/ /pubmed/33692756 http://dx.doi.org/10.3389/fendo.2021.620012 Text en Copyright © 2021 Vetrivel, Zhang, Engel, Altieri, Braun, Osswald, Bidlingmaier, Fassnacht, Beuschlein, Reincke, Chen, Sbiera and Riester http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Vetrivel, Sharmilee
Zhang, Ru
Engel, Mareen
Altieri, Barbara
Braun, Leah
Osswald, Andrea
Bidlingmaier, Martin
Fassnacht, Martin
Beuschlein, Felix
Reincke, Martin
Chen, Alon
Sbiera, Silviu
Riester, Anna
Circulating microRNA Expression in Cushing’s Syndrome
title Circulating microRNA Expression in Cushing’s Syndrome
title_full Circulating microRNA Expression in Cushing’s Syndrome
title_fullStr Circulating microRNA Expression in Cushing’s Syndrome
title_full_unstemmed Circulating microRNA Expression in Cushing’s Syndrome
title_short Circulating microRNA Expression in Cushing’s Syndrome
title_sort circulating microrna expression in cushing’s syndrome
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937959/
https://www.ncbi.nlm.nih.gov/pubmed/33692756
http://dx.doi.org/10.3389/fendo.2021.620012
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