Sharmilee Vetrivel1, Ru Zhang1, Mareen Engel2, Barbara Altieri3, Leah Braun1, Andrea Osswald1, Martin Bidlingmaier1, Martin Fassnacht3, Felix Beuschlein1,4, Martin Reincke1, Alon Chen2,5, Silviu Sbiera3, Anna Riester1. 1. Department of Endocrinology, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Germany. 2. Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany. 3. Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany. 4. Klinik für Endokrinologie, Diabetologie und Klinische Ernährung, Universitätsspital Zürich, Zürich, Switzerland. 5. Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
Abstract
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.
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.
Authors: E Patterson; R Webb; A Weisbrod; B Bian; M He; L Zhang; A K Holloway; R Krishna; N Nilubol; K Pacak; E Kebebew Journal: Endocr Relat Cancer Date: 2012-04-10 Impact factor: 5.678
Authors: Adrienn Zsippai; Diana Rita Szabó; Peter M Szabó; Zsófia Tömböl; Melinda R Bendes; Zoltán Nagy; Károly Rácz; Peter Igaz Journal: Am J Cancer Res Date: 2011-04-25 Impact factor: 6.166
Authors: German Rubinstein; Andrea Osswald; Eva Hoster; Marco Losa; Atanaska Elenkova; Sabina Zacharieva; Márcio Carlos Machado; Felicia Alexandra Hanzu; Stephanie Zopp; Katrin Ritzel; Anna Riester; Leah Theresa Braun; Ilonka Kreitschmann-Andermahr; Helen L Storr; Prachi Bansal; María-José Barahona; Elisa Cosaro; Sema Ciftci Dogansen; Philip C Johnston; Ricardo Santos de Oliveira; Christian Raftopoulos; Carla Scaroni; Elena Valassi; Steven J A van der Werff; Jochen Schopohl; Felix Beuschlein; Martin Reincke Journal: J Clin Endocrinol Metab Date: 2020-03-01 Impact factor: 5.958