Case Report: Micro-RNAs in Plasma From Bilateral Inferior Petrosal Sinus Sampling and Peripheral Blood From Corticotroph Pituitary Neuroendocrine Tumors

ObjectiveCirculating miRNAs are found in bodily fluids including plasma and can serve as biomarkers for diseases. The aim of this study was to provide the first insight into the landscape of circulating miRNAs in close proximity to the adrenocorticotropic hormone (ACTH) secreting PitNET. To achieve...

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Main Authors: Helvijs Niedra, Raitis Peculis, Ilze Konrade, Inga Balcere, Mihails Romanovs, Liva Steina, Janis Stukens, Jelizaveta Sokolovska, Janis Klovins, Vita Rovite
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-04-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2022.748152/full
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author Helvijs Niedra
Raitis Peculis
Ilze Konrade
Ilze Konrade
Inga Balcere
Inga Balcere
Mihails Romanovs
Mihails Romanovs
Liva Steina
Janis Stukens
Jelizaveta Sokolovska
Janis Klovins
Vita Rovite
author_facet Helvijs Niedra
Raitis Peculis
Ilze Konrade
Ilze Konrade
Inga Balcere
Inga Balcere
Mihails Romanovs
Mihails Romanovs
Liva Steina
Janis Stukens
Jelizaveta Sokolovska
Janis Klovins
Vita Rovite
author_sort Helvijs Niedra
collection DOAJ
description ObjectiveCirculating miRNAs are found in bodily fluids including plasma and can serve as biomarkers for diseases. The aim of this study was to provide the first insight into the landscape of circulating miRNAs in close proximity to the adrenocorticotropic hormone (ACTH) secreting PitNET. To achieve this objective next-generation sequencing of miRNAs in plasma from bilateral inferior petrosal sinus sampling (BIPSS) - a gold standard in diagnosing ACTH-secreting PitNETs was carried out and selected miRNA candidates were further tested by RT-qPCR in independent patient cohorts.MethodsSinistral (left) and dextral (right) BIPSS blood samples of the patient were collected in three time points: before the administration of corticotropin-releasing hormone, 5 and 15 minutes after stimulation. In differential expression analysis, sinistral plasma was compared with dextral. The selected miRNA candidates were tested in plasma by RT-qPCR in two patient groups: 1) in five ACTH secreting PitNET patients with plasma samples taken before and 24 hours after surgery, 2) in 12 ACTH secreting PitNET patients vs. 9 non-functioning PitNET patients.ResultsBIPSS concluded that the highest amount of ACTH was released in the sinistral side at the 5th minute mark indicating a presence of a tumor. The highest amount of differentially expressed miRNAs was observed 5 minutes after stimulation (20 upregulated, 14 downregulated). At the 5th minute mark in sinistral plasma, two miRNAs were identified: hsa-miR-7-5p and hsa-miR-375-3p that were highly upregulated compared to other BIPSS samples and peripheral plasma samples. Further testing by qPCR revealed significant reduction of miR-7-5p in plasma 24 hours after surgery and upregulation in plasma of ACTH secreting PitNET patients compared to non-functioning PitNET patients (P =0.0013).ConclusionsBy stimulating the ACTH secreting PitNET with CRH a rapid increase of two miRNAs (hsa-mir-7-5p, hsa-mir-375-3p) and ACTH can be observed in sinistral inferior petrosal (tumor side). A decrease of miR-7-5p in plasma after surgery and upregulation in plasma of ACTH secreting PitNET patients was discovered implying that further studies of this miRNA as diagnostic marker is needed.
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spelling doaj.art-f3fc6ffd29354bba8a281e54333045ff2022-12-22T02:39:20ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-04-011310.3389/fendo.2022.748152748152Case Report: Micro-RNAs in Plasma From Bilateral Inferior Petrosal Sinus Sampling and Peripheral Blood From Corticotroph Pituitary Neuroendocrine TumorsHelvijs Niedra0Raitis Peculis1Ilze Konrade2Ilze Konrade3Inga Balcere4Inga Balcere5Mihails Romanovs6Mihails Romanovs7Liva Steina8Janis Stukens9Jelizaveta Sokolovska10Janis Klovins11Vita Rovite12Department of Molecular and Functional Genomics, Latvian Biomedical Research and Study Centre, Riga, LatviaDepartment of Molecular and Functional Genomics, Latvian Biomedical Research and Study Centre, Riga, LatviaDepartment of Endocrinology, Riga East Clinical University Hospital, Riga, LatviaDepartment of Internal Diseases, Riga Stradins University, Riga, LatviaDepartment of Endocrinology, Riga East Clinical University Hospital, Riga, LatviaDepartment of Internal Diseases, Riga Stradins University, Riga, LatviaDepartment of Endocrinology, Riga East Clinical University Hospital, Riga, LatviaDepartment of Internal Diseases, Riga Stradins University, Riga, LatviaDepartment of Neurosurgery, Pauls Stradins Clinical University Hospital, Riga, LatviaDepartment of Neurosurgery, Pauls Stradins Clinical University Hospital, Riga, LatviaUniversity of Latvia Faculty of Medicine, Riga, LatviaDepartment of Molecular and Functional Genomics, Latvian Biomedical Research and Study Centre, Riga, LatviaDepartment of Molecular and Functional Genomics, Latvian Biomedical Research and Study Centre, Riga, LatviaObjectiveCirculating miRNAs are found in bodily fluids including plasma and can serve as biomarkers for diseases. The aim of this study was to provide the first insight into the landscape of circulating miRNAs in close proximity to the adrenocorticotropic hormone (ACTH) secreting PitNET. To achieve this objective next-generation sequencing of miRNAs in plasma from bilateral inferior petrosal sinus sampling (BIPSS) - a gold standard in diagnosing ACTH-secreting PitNETs was carried out and selected miRNA candidates were further tested by RT-qPCR in independent patient cohorts.MethodsSinistral (left) and dextral (right) BIPSS blood samples of the patient were collected in three time points: before the administration of corticotropin-releasing hormone, 5 and 15 minutes after stimulation. In differential expression analysis, sinistral plasma was compared with dextral. The selected miRNA candidates were tested in plasma by RT-qPCR in two patient groups: 1) in five ACTH secreting PitNET patients with plasma samples taken before and 24 hours after surgery, 2) in 12 ACTH secreting PitNET patients vs. 9 non-functioning PitNET patients.ResultsBIPSS concluded that the highest amount of ACTH was released in the sinistral side at the 5th minute mark indicating a presence of a tumor. The highest amount of differentially expressed miRNAs was observed 5 minutes after stimulation (20 upregulated, 14 downregulated). At the 5th minute mark in sinistral plasma, two miRNAs were identified: hsa-miR-7-5p and hsa-miR-375-3p that were highly upregulated compared to other BIPSS samples and peripheral plasma samples. Further testing by qPCR revealed significant reduction of miR-7-5p in plasma 24 hours after surgery and upregulation in plasma of ACTH secreting PitNET patients compared to non-functioning PitNET patients (P =0.0013).ConclusionsBy stimulating the ACTH secreting PitNET with CRH a rapid increase of two miRNAs (hsa-mir-7-5p, hsa-mir-375-3p) and ACTH can be observed in sinistral inferior petrosal (tumor side). A decrease of miR-7-5p in plasma after surgery and upregulation in plasma of ACTH secreting PitNET patients was discovered implying that further studies of this miRNA as diagnostic marker is needed.https://www.frontiersin.org/articles/10.3389/fendo.2022.748152/fullmicro-RNA differential expressionbilateral inferior petrosal sinus samplingcirculating plasma micro-RNAscorticotroph pituitary neuroendocrine tumorCushing’s disease
spellingShingle Helvijs Niedra
Raitis Peculis
Ilze Konrade
Ilze Konrade
Inga Balcere
Inga Balcere
Mihails Romanovs
Mihails Romanovs
Liva Steina
Janis Stukens
Jelizaveta Sokolovska
Janis Klovins
Vita Rovite
Case Report: Micro-RNAs in Plasma From Bilateral Inferior Petrosal Sinus Sampling and Peripheral Blood From Corticotroph Pituitary Neuroendocrine Tumors
Frontiers in Endocrinology
micro-RNA differential expression
bilateral inferior petrosal sinus sampling
circulating plasma micro-RNAs
corticotroph pituitary neuroendocrine tumor
Cushing’s disease
title Case Report: Micro-RNAs in Plasma From Bilateral Inferior Petrosal Sinus Sampling and Peripheral Blood From Corticotroph Pituitary Neuroendocrine Tumors
title_full Case Report: Micro-RNAs in Plasma From Bilateral Inferior Petrosal Sinus Sampling and Peripheral Blood From Corticotroph Pituitary Neuroendocrine Tumors
title_fullStr Case Report: Micro-RNAs in Plasma From Bilateral Inferior Petrosal Sinus Sampling and Peripheral Blood From Corticotroph Pituitary Neuroendocrine Tumors
title_full_unstemmed Case Report: Micro-RNAs in Plasma From Bilateral Inferior Petrosal Sinus Sampling and Peripheral Blood From Corticotroph Pituitary Neuroendocrine Tumors
title_short Case Report: Micro-RNAs in Plasma From Bilateral Inferior Petrosal Sinus Sampling and Peripheral Blood From Corticotroph Pituitary Neuroendocrine Tumors
title_sort case report micro rnas in plasma from bilateral inferior petrosal sinus sampling and peripheral blood from corticotroph pituitary neuroendocrine tumors
topic micro-RNA differential expression
bilateral inferior petrosal sinus sampling
circulating plasma micro-RNAs
corticotroph pituitary neuroendocrine tumor
Cushing’s disease
url https://www.frontiersin.org/articles/10.3389/fendo.2022.748152/full
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