Circulating Plasma MicroRNA in Patients With Active Acromegaly

Lutsenko, Alexander; Belaya, Zhanna; Nikitin, Alexey; Solodovnikov, Alexander; Лапшина, А М; Koshkin, Philipp; Воронцова, М. А.; Rozhinskaya, Liudmila; Melnichenko, Galina; Дедов, И И

doi:10.1210/clinem/dgab695

Cited by 5 publications

(4 citation statements)

References 45 publications

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“…В то же время в исследовании Lutsenko A. и соавт. при сравнении профиля экспрессии микроРНК пациентов со спорадической акромегалией и контролем было выявлено снижение уровней miR-4446-3p и miR-215‐5p в группе акромегалии по сравнению с контролем [ 29 ], что может объяснять сниженную экспрессию miR-215‐5p в группе фМЭН-1, учитывая наличие акромегалии у всех пациентов в этой группе. Усиление экспрессии miR-215‐5p может быть связано также со злокачественными новообразованиями, так, например, повышение экспрессии miR-215‐5p выявлено у пациентов с аденокарциномой протоков поджелудочной железы [ 30 ], с раком желудка [ 31 ], пациентов с остеосаркомой по сравнению с контролем [ 32 ] и у пациентов с раком молочной железы по сравнению с контрольной группой [ 33 ].…”

Section: Discussionunclassified

Plasma miRNA expression in patients with genetically confirmed multiple endocrine neoplasia type 1 syndrome and its phenocopies

Trukhina,

Mamedova,

Nikitin

et al. 2024

Probl Endokrinol (Mosk)

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BACKGROUND: MEN-1 is a rare autosomal dominant disease caused by mutations in MEN1 gene encoding the menin protein. This syndrome is characterized by the occurrence of parathyroid tumors, gastroenteropancreatic neuroendocrine tumors, pituitary adenomas, as well as other endocrine and non-endocrine tumors. If a patient with the MEN-1 phenotype carry no mutations in the MEN1 gene, the condition considers a phenocopy of syndrome (phMEN1). The possible cause of this changes could be changes in epigenetic regulation, particularly in microRNA expression that might affect menin signaling pathways.AIM: to identify differently expressed circulating miRNAs in plasma in patients with genetically confirmed MEN-1 syndrome, its phenocopies and healthy controls.MATERIALS AND METHODS: single-center, case-control study was conducted. We assessed plasma microRNA expression in patients with genetically confirmed MEN-1 (gMEN1), phMEN1 and healthy controls. Morning plasma samples were collected from fasting patients and stored at –80°C. Total RNA isolation was performed using miRNeasy Mini Kit with QIAcube. The libraries were prepared by the QIAseq miRNA Library Kit following the manufacturer. Circulating miRNA sequencing was done on Illumina NextSeq 500 (Illumina). Subsequent data processing was performed using the DESeq2 bioinformatics algorithm.RESULTS: we enrolled 21 consecutive patients with gMEN1 and 11 patients with phMEN1, along with 12 gender matched controls. Median age of gMEN1 was 38,0 [34,0; 41,0]; in phMEN1 — 59,0 [51,0; 60,0]; control — 59,5 [51,5; 62,5]. The gMEN1 group differed in age (p<0.01) but not gender (р=0.739) or BMI (р=0.116) compared to phMEN1 and controls group, the last two groups did not differ by these parameters (p>0.05). 25 microRNA were differently expressed in groups gMEN1 and phMEN1 (21 upregulated microRNAs, 4 — downregulated). Comparison of samples from the phMEN-1 group and relatively healthy controls revealed 10 differently expressed microRNAs: 5 — upregulated; 5 — downregulated. In the gMEN-1 and control groups, 26 differently expressed microRNAs were found: 24 — upregulated; 2 — downregulated. The miRNAs most differing in expression among the groups were selected for further validation by RT-qPCR (in the groups of gMEN1 vs phMEN1 — miR-3613-5p, miR-335-5p, miR-32-5p, miR-425-3p, miR-25-5p, miR-576-5p, miR-215-5p, miR-30a-3p, miR-141-3p, miR-760, miR-501-3p; gMEN1 vs control — miR-1976, miR-144-5p miR-532-3p, miR-375; as well as in phMEN1 vs control — miR-944, miR-191-5p, miR-98-5p).CONCLUSION: In a pilot study, we detected microRNAs that may be expressed differently between patients with gMEN-1 and phMEN-1. The results need to be validated using different measurement method with larger sample size.

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Section: Discussionunclassified

Plasma miRNA expression in patients with genetically confirmed multiple endocrine neoplasia type 1 syndrome and its phenocopies

Trukhina,

Mamedova,

Nikitin

et al. 2024

Probl Endokrinol (Mosk)

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“…Another study found downregulated plasma miR-4446-3p and miR-215-5p in patients with acromegaly compared to healthy subjects [ 95 ]. Both miRNAs were correlated with IGF-I levels, suggesting its association with biochemical features.…”

Section: Circulating Mirnas In Acromegalymentioning

confidence: 99%

“…Both miRNAs were correlated with IGF-I levels, suggesting its association with biochemical features. These circulating miRNA’s origin is unknown, and its overexpression may only be a consequence of high GH and IGF-I levels rather than being secreted from the pituitary adenoma [ 95 ]. MiR-215-5p is downregulated in colorectal cancer tissues, possibly acting as a tumor suppressor [ 96 ].…”

Section: Circulating Mirnas In Acromegalymentioning

confidence: 99%

MicroRNA in Acromegaly: Involvement in the Pathogenesis and in the Response to First-Generation Somatostatin Receptor Ligands

Henriques

Lamback

Dezonne

et al. 2022

IJMS

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Acromegaly is a chronic and systemic disease due to excessive growth hormone and insulin-like growth factor type I caused, in the vast majority of cases, by a GH-secreting pituitary adenoma. About 40% of these tumors have somatic mutations in the stimulatory G protein alpha-subunit 1 gene. The pathogenesis of the remaining tumors, however, is still not fully comprehended. Surgery is the first-line therapy for these tumors, and first-generation somatostatin receptor ligands (fg-SRL) are the most prescribed medications in patients who are not cured by surgery. MicroRNAs are small, non-coding RNAs that control the translation of many mRNAs, and are involved in the post-transcriptional regulation of gene expression. Differentially expressed miRNAs can explain differences in the pathogenesis of acromegaly and tumor resistance. In this review, we focus on the most validated miRNAs, which are mainly involved in acromegaly’s tumorigenesis and fg-SRL resistance, as well as in circulating miRNAs in acromegaly.

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“…МикроРНК в данной когорте ранее изучались в двухэтапном исследовании [ 8 ][ 9 ]. В настоящем исследовании проведена оценка уровней микроРНК у пациентов в зависимости от достижения краткосрочной и долгосрочной ремиссии после нейрохирургического вмешательства.…”

Section: генетические исследованияunclassified

Short-term and long-term remission after endoscopic transnasal adenomectomy in patients with acromegaly

Lutsenko

Belaya

Przhiyalkovskaya

et al. 2022

Probl Endokrinol (Mosk)

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BACKGROUND. Neurosurgery is the most effective treatment for acromegaly. As most of the patients present with macroadenomas, surgical treatment is not always successful, even with the expert level of a neurosurgeon. Assessment of the postoperative remission rates in acromegaly preoperative predictors of treatment efficacy is an urgent task of modern research. AIM: To assess the short-term and long-term remission of acromegaly after endoscopic transnasal adenomectomy in a tertiary medical center and assess preoperative predictors of the treatment effectiveness.MATERIALS AND METHODS: A single-center, prospective, uncontrolled study was conducted. We included patients with active acromegaly who did not receive medical therapy with somatostatin analogues and were referred for endoscopic transsphenoidal adenomectomy. Plasma miRNA expression was assessed by quantitative reverse transcription PCR. Postoperative samples of adenomas were sent for study, with the determination of the immunohistochemical staining for somatostatin receptors 2 and 5 subtypes and morphology was performed on postoperative adenoma samples.RESULTS: The study included 44 patients: 32.8% men, median age 47.0 [34.0; 55.0], IGF-1 744.75 ng/ml [548.83;889.85], growth hormone 9.5 ng/ml [4.94; 17.07]. Tumor volume 832 mm3 [419.25; 2532.38]. Early postoperative remission was achieved in 35 patients (79.5%). Patients who achieved short-term remission had higher IGF-1 and basal growth hormone levels. Median follow-up was 19.0 months [12.5;29.0]. Long-term remission was achieved in 61.4% (27 patients), no remission in 9 (20.5%), recurrency in 2 patients (4.5%), 6 patients were to follow-up (13.6%). In patients with long-term remission, we observed lower growth hormone and IGF-1 levels. No differences in miRNA expression was observesd. The predictive value of basal GH before surgery for long-term remission was assessed: area under the curve 0.811 (95% CI: 0.649; 0.973). A cut-off value of 15.55 ng/mL corresponded to a sensitivity of 70.0% (34.8%; 93.3%), a specificity of 85.7% (67.3%; 96.0%), an accuracy of 81.6% (65 .7%; 92.3%), PPV 63.6% (39.3%; 82.5%), NPV 88.9% (75.4%; 95.4%).CONCLUSION: Rates of short-term and long-term remission after endoscopic transsphenoidal adenomectomy in our cohort is 79,5% и 61,4%, respectively, and is comparable with literature data for expert pituitary centers. Preoperative GH shows potential value in predicting the long-term remission of acromegaly, but further studies in a larger sample are needed to obtain more accurate cut-off values.

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Circulating Plasma MicroRNA in Patients With Active Acromegaly

Cited by 5 publications

References 45 publications

Plasma miRNA expression in patients with genetically confirmed multiple endocrine neoplasia type 1 syndrome and its phenocopies

Plasma miRNA expression in patients with genetically confirmed multiple endocrine neoplasia type 1 syndrome and its phenocopies

MicroRNA in Acromegaly: Involvement in the Pathogenesis and in the Response to First-Generation Somatostatin Receptor Ligands

Short-term and long-term remission after endoscopic transnasal adenomectomy in patients with acromegaly

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