Circulating Plasma microRNA to Differentiate Cushing's Disease From Ectopic ACTH Syndrome
Corticotropinomas and adrenocorticotropic hormone (ACTH)-secreting neuroendocrine tumors exhibit differential levels of some microRNAs (miRs) compared to normal tissue. Because miRs can be released from tissues into circulation, they offer promise as novel disease biomarkers.Objective: To evaluate w...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-06-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2020.00331/full |
| _version_ | 1818533744687972352 |
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| author | Zhanna Belaya Patimat Khandaeva Larisa Nonn Alexey Nikitin Alexander Solodovnikov Ivan Sitkin Andrey Grigoriev Mikhail Pikunov Anastasia Lapshina Liudmila Rozhinskaya Galina Melnichenko Ivan Dedov |
| author_facet | Zhanna Belaya Patimat Khandaeva Larisa Nonn Alexey Nikitin Alexander Solodovnikov Ivan Sitkin Andrey Grigoriev Mikhail Pikunov Anastasia Lapshina Liudmila Rozhinskaya Galina Melnichenko Ivan Dedov |
| author_sort | Zhanna Belaya |
| collection | DOAJ |
| description | Corticotropinomas and adrenocorticotropic hormone (ACTH)-secreting neuroendocrine tumors exhibit differential levels of some microRNAs (miRs) compared to normal tissue. Because miRs can be released from tissues into circulation, they offer promise as novel disease biomarkers.Objective: To evaluate whether miRs are differentially detected in plasma samples of patients with ACTH-dependent Cushing's syndrome (CS).Design: Case-control study.Methods: Morning fasting plasma samples were collected from 41 consecutive patients with confirmed ACTH-dependent CS and 11 healthy subjects and stored at −80°C. Twenty-one miRs previously reported to be differentially expressed in ACTH-secreting tumors vs. healthy tissue samples were quantified in plasma by qPCR.Results: Among enrolled subjects, 28 were confirmed to have Cushing's disease (CD), 13 had ectopic ACTH secretion (EAS) and 11 were healthy controls. We found statistically significant differences in the circulating levels of miR-16-5p [45.04 (95% CI 28.77–61.31) in CD vs. 5.26 (2.65–7.87) in EAS, P < 0.001; q = 0.001], miR-145-5p [0.097 (0.027–0.167) in CD vs. undetectable levels in EAS, P = 0.008; q = 0.087] and differences in miR-7g-5p [1.842 (1.283–2.400) in CD vs. 0.847 (0.187–1.507) in EAS, P = 0.02; q = 0.14]. The area under the receiver-operator (ROC) curve was 0.879 (95% CI 0.770–0.987), p < 0.001, when using miR-16-5p to distinguish between CD and EAS. Circulating levels of miR-16-5p in the healthy control group differed from that of both the CD and EAS groups.Conclusions: Plasma miR levels differ in patients with CD and EAS. In particular, miR-16-5p, miR-145-5p and miR-7g-5p are promising biomarkers for further research to differentiate ACTH-dependent CS. |
| first_indexed | 2024-12-11T18:02:47Z |
| format | Article |
| id | doaj.art-30456808dca24f7486bc66bc050f1564 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-11T18:02:47Z |
| publishDate | 2020-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-30456808dca24f7486bc66bc050f15642022-12-22T00:55:49ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922020-06-011110.3389/fendo.2020.00331535547Circulating Plasma microRNA to Differentiate Cushing's Disease From Ectopic ACTH SyndromeZhanna Belaya0Patimat Khandaeva1Larisa Nonn2Alexey Nikitin3Alexander Solodovnikov4Ivan Sitkin5Andrey Grigoriev6Mikhail Pikunov7Anastasia Lapshina8Liudmila Rozhinskaya9Galina Melnichenko10Ivan Dedov11The National Medical Research Centre for Endocrinology, Moscow, RussiaThe National Medical Research Centre for Endocrinology, Moscow, RussiaDepartment Pathology College of Medicine, University of Illinois at Chicago, Chicago, IL, United StatesFederal Research and Clinical Center FMBA of Russia, Moscow, RussiaUral State Medical Academy, Yekaterinburg, RussiaThe National Medical Research Centre for Endocrinology, Moscow, RussiaThe National Medical Research Centre for Endocrinology, Moscow, RussiaNational Medical Research Center of Surgery Named After A.V. Vishnevsky, Moscow, RussiaThe National Medical Research Centre for Endocrinology, Moscow, RussiaThe National Medical Research Centre for Endocrinology, Moscow, RussiaThe National Medical Research Centre for Endocrinology, Moscow, RussiaThe National Medical Research Centre for Endocrinology, Moscow, RussiaCorticotropinomas and adrenocorticotropic hormone (ACTH)-secreting neuroendocrine tumors exhibit differential levels of some microRNAs (miRs) compared to normal tissue. Because miRs can be released from tissues into circulation, they offer promise as novel disease biomarkers.Objective: To evaluate whether miRs are differentially detected in plasma samples of patients with ACTH-dependent Cushing's syndrome (CS).Design: Case-control study.Methods: Morning fasting plasma samples were collected from 41 consecutive patients with confirmed ACTH-dependent CS and 11 healthy subjects and stored at −80°C. Twenty-one miRs previously reported to be differentially expressed in ACTH-secreting tumors vs. healthy tissue samples were quantified in plasma by qPCR.Results: Among enrolled subjects, 28 were confirmed to have Cushing's disease (CD), 13 had ectopic ACTH secretion (EAS) and 11 were healthy controls. We found statistically significant differences in the circulating levels of miR-16-5p [45.04 (95% CI 28.77–61.31) in CD vs. 5.26 (2.65–7.87) in EAS, P < 0.001; q = 0.001], miR-145-5p [0.097 (0.027–0.167) in CD vs. undetectable levels in EAS, P = 0.008; q = 0.087] and differences in miR-7g-5p [1.842 (1.283–2.400) in CD vs. 0.847 (0.187–1.507) in EAS, P = 0.02; q = 0.14]. The area under the receiver-operator (ROC) curve was 0.879 (95% CI 0.770–0.987), p < 0.001, when using miR-16-5p to distinguish between CD and EAS. Circulating levels of miR-16-5p in the healthy control group differed from that of both the CD and EAS groups.Conclusions: Plasma miR levels differ in patients with CD and EAS. In particular, miR-16-5p, miR-145-5p and miR-7g-5p are promising biomarkers for further research to differentiate ACTH-dependent CS.https://www.frontiersin.org/article/10.3389/fendo.2020.00331/fullcirculating microRNACushing's diseaseectopic ACTH syndromemicroRNA-16-5pACTH dependent Cushing's syndrome |
| spellingShingle | Zhanna Belaya Patimat Khandaeva Larisa Nonn Alexey Nikitin Alexander Solodovnikov Ivan Sitkin Andrey Grigoriev Mikhail Pikunov Anastasia Lapshina Liudmila Rozhinskaya Galina Melnichenko Ivan Dedov Circulating Plasma microRNA to Differentiate Cushing's Disease From Ectopic ACTH Syndrome Frontiers in Endocrinology circulating microRNA Cushing's disease ectopic ACTH syndrome microRNA-16-5p ACTH dependent Cushing's syndrome |
| title | Circulating Plasma microRNA to Differentiate Cushing's Disease From Ectopic ACTH Syndrome |
| title_full | Circulating Plasma microRNA to Differentiate Cushing's Disease From Ectopic ACTH Syndrome |
| title_fullStr | Circulating Plasma microRNA to Differentiate Cushing's Disease From Ectopic ACTH Syndrome |
| title_full_unstemmed | Circulating Plasma microRNA to Differentiate Cushing's Disease From Ectopic ACTH Syndrome |
| title_short | Circulating Plasma microRNA to Differentiate Cushing's Disease From Ectopic ACTH Syndrome |
| title_sort | circulating plasma microrna to differentiate cushing s disease from ectopic acth syndrome |
| topic | circulating microRNA Cushing's disease ectopic ACTH syndrome microRNA-16-5p ACTH dependent Cushing's syndrome |
| url | https://www.frontiersin.org/article/10.3389/fendo.2020.00331/full |
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