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Published on: February 12, 2018
Circulating Plasma MicroRNA in Patients With Active Acromegaly
Alexander Lutsenko1, Zhanna Belaya1, Alexey Nikitin2
1Department of Neuroendocrinology and Bone Diseases, Endocrinology Research Centre, Moscow, Russia.
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.
