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.