Circulating MicroRNAs as Non-invasive Biomarkers for Canine Cushing's Syndrome
Canine Cushing's syndrome (hypercortisolism) can be caused by a pituitary tumor (pituitary-dependent hypercortisolism; PDH) or a cortisol-secreting adrenocortical tumor (csACT). For both cases, non-invasive biomarkers that could pre-operatively predict the risk of recurrence after surgery would...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Veterinary Science |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fvets.2021.760487/full |
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| author | Karin Sanders Anouk Veldhuizen Hans S. Kooistra Adri Slob Elpetra P. M. Timmermans-Sprang Frank M. Riemers Sylvie Daminet Federico Fracassi Sebastiaan A. van Nimwegen Björn P. Meij Sara Galac |
| author_facet | Karin Sanders Anouk Veldhuizen Hans S. Kooistra Adri Slob Elpetra P. M. Timmermans-Sprang Frank M. Riemers Sylvie Daminet Federico Fracassi Sebastiaan A. van Nimwegen Björn P. Meij Sara Galac |
| author_sort | Karin Sanders |
| collection | DOAJ |
| description | Canine Cushing's syndrome (hypercortisolism) can be caused by a pituitary tumor (pituitary-dependent hypercortisolism; PDH) or a cortisol-secreting adrenocortical tumor (csACT). For both cases, non-invasive biomarkers that could pre-operatively predict the risk of recurrence after surgery would greatly impact clinical decision making. The aim of this study was to determine whether circulating microRNAs (miRNAs) can be used as diagnostic (presence of PDH or csACT) and/or prognostic (disease recurrence, histological grade) non-invasive biomarkers for canine Cushing's syndrome. After a pilot study with 40 miRNAs in blood samples of healthy dogs (n = 3), dogs with PDH (n = 3) and dogs with a csACT (n = 4), we selected a total of 20 miRNAs for the definitive study. In the definitive study, these 20 miRNAs were analyzed in blood samples of healthy dogs (n = 6), dogs with PDH (n = 19, pre- and post-operative samples) and dogs with a csACT (n = 26, pre-operative samples). In dogs with PDH, six miRNAs (miR-122-5p, miR-126-5p, miR-141-3p, miR-222-3p, miR-375-3p and miR-483-3p) were differentially expressed compared to healthy dogs. Of one miRNA, miR-122-5p, the expression levels did not overlap between healthy dogs and dogs with PDH (p = 2.9x10−4), significantly decreased after hypophysectomy (p = 0.013), and were significantly higher (p = 0.017) in dogs with recurrence (n = 3) than in dogs without recurrence for at least one year after hypophysectomy (n = 7). In dogs with csACTs, two miRNAs (miR-483-3p and miR-223-3p) were differentially expressed compared to healthy dogs. Additionally, miR-141-3p was expressed significantly lower (p = 0.009) in dogs with csACTs that had a histopathological Utrecht score of ≥ 11 compared to those with a score of <11. These results indicate that circulating miRNAs have the potential to be non-invasive biomarkers in dogs with Cushing's syndrome that may contribute to clinical decision making. |
| first_indexed | 2024-12-20T19:15:23Z |
| format | Article |
| id | doaj.art-269ddf2aae4b4e2c8678a767f0a369a1 |
| institution | Directory Open Access Journal |
| issn | 2297-1769 |
| language | English |
| last_indexed | 2024-12-20T19:15:23Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Veterinary Science |
| spelling | doaj.art-269ddf2aae4b4e2c8678a767f0a369a12022-12-21T19:29:08ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692021-11-01810.3389/fvets.2021.760487760487Circulating MicroRNAs as Non-invasive Biomarkers for Canine Cushing's SyndromeKarin Sanders0Anouk Veldhuizen1Hans S. Kooistra2Adri Slob3Elpetra P. M. Timmermans-Sprang4Frank M. Riemers5Sylvie Daminet6Federico Fracassi7Sebastiaan A. van Nimwegen8Björn P. Meij9Sara Galac10Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, NetherlandsDepartment of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, NetherlandsDepartment of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, NetherlandsDepartment of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, NetherlandsDepartment of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, NetherlandsDepartment of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, NetherlandsSmall Animal Department, Faculty of Veterinary Medicine, Ghent University, Merelbeke, BelgiumDepartment of Veterinary Medical Sciences, University of Bologna, Ozzano dell'Emilia, Bologna, ItalyDepartment of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, NetherlandsDepartment of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, NetherlandsDepartment of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, NetherlandsCanine Cushing's syndrome (hypercortisolism) can be caused by a pituitary tumor (pituitary-dependent hypercortisolism; PDH) or a cortisol-secreting adrenocortical tumor (csACT). For both cases, non-invasive biomarkers that could pre-operatively predict the risk of recurrence after surgery would greatly impact clinical decision making. The aim of this study was to determine whether circulating microRNAs (miRNAs) can be used as diagnostic (presence of PDH or csACT) and/or prognostic (disease recurrence, histological grade) non-invasive biomarkers for canine Cushing's syndrome. After a pilot study with 40 miRNAs in blood samples of healthy dogs (n = 3), dogs with PDH (n = 3) and dogs with a csACT (n = 4), we selected a total of 20 miRNAs for the definitive study. In the definitive study, these 20 miRNAs were analyzed in blood samples of healthy dogs (n = 6), dogs with PDH (n = 19, pre- and post-operative samples) and dogs with a csACT (n = 26, pre-operative samples). In dogs with PDH, six miRNAs (miR-122-5p, miR-126-5p, miR-141-3p, miR-222-3p, miR-375-3p and miR-483-3p) were differentially expressed compared to healthy dogs. Of one miRNA, miR-122-5p, the expression levels did not overlap between healthy dogs and dogs with PDH (p = 2.9x10−4), significantly decreased after hypophysectomy (p = 0.013), and were significantly higher (p = 0.017) in dogs with recurrence (n = 3) than in dogs without recurrence for at least one year after hypophysectomy (n = 7). In dogs with csACTs, two miRNAs (miR-483-3p and miR-223-3p) were differentially expressed compared to healthy dogs. Additionally, miR-141-3p was expressed significantly lower (p = 0.009) in dogs with csACTs that had a histopathological Utrecht score of ≥ 11 compared to those with a score of <11. These results indicate that circulating miRNAs have the potential to be non-invasive biomarkers in dogs with Cushing's syndrome that may contribute to clinical decision making.https://www.frontiersin.org/articles/10.3389/fvets.2021.760487/fullmiRNApituitary-dependent hypercortisolismCushing's diseaseadrenocortical tumormiR-122prognostic |
| spellingShingle | Karin Sanders Anouk Veldhuizen Hans S. Kooistra Adri Slob Elpetra P. M. Timmermans-Sprang Frank M. Riemers Sylvie Daminet Federico Fracassi Sebastiaan A. van Nimwegen Björn P. Meij Sara Galac Circulating MicroRNAs as Non-invasive Biomarkers for Canine Cushing's Syndrome Frontiers in Veterinary Science miRNA pituitary-dependent hypercortisolism Cushing's disease adrenocortical tumor miR-122 prognostic |
| title | Circulating MicroRNAs as Non-invasive Biomarkers for Canine Cushing's Syndrome |
| title_full | Circulating MicroRNAs as Non-invasive Biomarkers for Canine Cushing's Syndrome |
| title_fullStr | Circulating MicroRNAs as Non-invasive Biomarkers for Canine Cushing's Syndrome |
| title_full_unstemmed | Circulating MicroRNAs as Non-invasive Biomarkers for Canine Cushing's Syndrome |
| title_short | Circulating MicroRNAs as Non-invasive Biomarkers for Canine Cushing's Syndrome |
| title_sort | circulating micrornas as non invasive biomarkers for canine cushing s syndrome |
| topic | miRNA pituitary-dependent hypercortisolism Cushing's disease adrenocortical tumor miR-122 prognostic |
| url | https://www.frontiersin.org/articles/10.3389/fvets.2021.760487/full |
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