Circulating Plasma MicroRNA in Patients With Active Acromegaly
| Autor: | Philipp Koshkin, Anastasia Lapshina, Alexey Nikitin, Zhanna E. Belaya, Alexander Solodovnikov, Ivan Ivanovich Dedov, Maria Vorontsova, Liudmila Rozhinskaya, Alexander Lutsenko, Galina A. Melnichenko |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Oncology medicine.medical_specialty Endocrinology Diabetes and Metabolism Clinical Biochemistry Down-Regulation Context (language use) Growth hormone Biochemistry Young Adult Endocrinology Internal medicine microRNA Acromegaly medicine Humans In patient Circulating MicroRNA Human Growth Hormone Reverse Transcriptase Polymerase Chain Reaction business.industry Biochemistry (medical) Healthy subjects Middle Aged medicine.disease Healthy Volunteers MicroRNAs Cross-Sectional Studies Case-Control Studies Cohort Female business Biomarkers |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 107:500-511 |
| ISSN: | 1945-7197 0021-972X |
| Popis: | 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 sex-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 miRNAs were quantified by next-generation sequencing (NGS) in the discovery phase. Levels of selected miRNAs were validated on extended cohorts using reverse transcription quantitative polymerase chain reaction (RT-qPCR), compared between groups, and correlated with clinical parameters. Results Based on NGS data, we selected 3 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), and miR-342-5p −1.875 (P = 0.013) without multiplicity correction for all 3 miRNAs. These results were confirmed by RT-qPCR in the validation phase for 2 miRNAs out of 3: miR-4446-3p (P < 0.001, Padjusted < 0.001), area under the receiver-operator curve (AUC) 0.862 (95% CI 0.723-0.936; P < 0.001) and miR-215-5p (P < 0.001, Padjusted < 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 2-phase experiment using 2 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|