Expression of plasma microRNA in patients with acromegaly

Луценко, Александр Сергеевич; Белая, Жанна Евгеньевна; Пржиялковская, Е. Г.; Никитин, Алексей Георгиевич; Koshkin, F. A.; Лапшина, Анастасия Михайловна; Khandaeva, Patimat; Мельниченко, Г. А.

doi:10.14341/probl10263

Cited by 5 publications

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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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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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“…Using next-generation sequencing (NGS), Lutsenko et al performed profiling on four circulating miRNAs (miR-4446-3p, miR-215-5p, miR-342-5p, and miR-191-5p) in the plasma of 12 patients with acromegaly compared with 12 healthy controls [ 55 ]. They found decreased expression of these four circulating miRNAs.…”

Section: Circulating Mirnas and Pamentioning

confidence: 99%

MiRNAs as Noninvasive Biomarkers and Therapeutic Agents of Pituitary Adenomas

Beylerli

Beeraka

Gareev

et al. 2020

IJMS

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Pituitary adenoma (PA) accounts for 10–15% of all intracranial neoplasms. Even though most pituitary adenomas are benign, it is known that almost 35% of them exhibit an aggressive clinical course, including rapid proliferative activity and invasion of neighboring tissues. MicroRNAs (miRNAs) are short single-stranded RNA molecules that can influence post-transcriptional regulation by controlling target genes. Based on research data on miRNAs over the past 20 years, more than 60% of genes encoding human proteins are regulated by miRNAs, which ultimately control basic cellular mechanisms, including cell proliferation, differentiation, and apoptosis. Dysregulation of miRNAs has been observed in a number of diseases, especially tumors like PA. A majority of miRNAs are expressed within the cells themselves. However, the circulating miRNAs can be detected in several biological fluids of the human body. The identification of circulating miRNAs as new molecular markers may increase the ability to detect a tumor, predict the course of a disease, plan to choose suitable treatment, and diagnose at the earliest signs of impending neoplastic transformation. Therapy of PAs with aggressive behavior is a complex task. When surgery and chemotherapy fail, radiotherapy becomes the treatment of choice against PAs. Therefore, the possibility of implementing circulating miRNAs as innovative diagnostic and therapeutic agents for PA is one of the main exciting ideas.

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Circulating Plasma MicroRNA in Patients With Active Acromegaly

Lutsenko¹,

Belaya²,

Nikitin

et al. 2021

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context Excessive production of growth hormone causes marked multiorgan changes in patients with acromegaly, which may involve epigenetic mechanisms. Objective To evaluate differences in circulating microRNAs (miRNAs) associated with chronic growth hormone overproduction in adults. Design and setting A cross-sectional case-control study was conducted at a tertiary medical center. Participants We enrolled 12 consecutive patients with acromegaly along with 12 age and gender matched controls in the discovery phase of the study and then extended this cohort to 47 patients with acromegaly and 28 healthy controls for the validation study. Main Outcome Measures Plasma microRNAs were quantified by next-generation sequencing (NGS) in the discovery phase. Levels of selected miRNAs were validated on extended cohorts using RT-qPCR, compared between groups and correlated with clinical parameters. Results Based on NGS data, we selected three plasma miRNAs downregulated in patients with acromegaly compared to healthy controls: miR-4446-3p –1.317 (p=0.001), miR-215-5p –3.040 (p=0.005), miR-342-5p –1.875 (p=0.013) without multiplicity correction for all three miRNAs. These results were confirmed by RT-qPCR in the validation phase for two miRNAs out of three: miR-4446-3p (p <0.001, p-adj <0.001), AUC 0.862 (95% CI 0.723-0.936) p<0.001 and miR-215-5p (p <0.001, p-adj <0.001), AUC 0.829 (95% CI 0.698-0.907) p<0.001 to differentiate patients with acromegaly from healthy controls. Conclusions In a two-phase experiment using two different techniques we found and validated the downregulation of plasma miR-4446-3p and miR-215-5p in patients with acromegaly compared to healthy subjects, which makes them promising biomarkers for further research.

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Expression of plasma microRNA in patients with acromegaly

Cited by 5 publications

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

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

MiRNAs as Noninvasive Biomarkers and Therapeutic Agents of Pituitary Adenomas

Circulating Plasma MicroRNA in Patients With Active Acromegaly

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