Discovery and validation of circulating Hsa-miR-210-3p as a potential biomarker for primary open-angle glaucoma

Abstract

PURPOSE. Blood-based examination tools for glaucoma diagnosis in clinical practice, which can be useful for screening patients when traditional ophthalmic examinations cannot be utilized, are not available thus far. This study aimed to identify circulating microRNAs (miRNAs) associated with primary open-angle glaucoma (POAG) and explore their utility as diagnostic markers. METHODS. A total of 136 POAG patients and controls were enrolled. Next-generation RNA sequencing was used to explore the expression profile of circulating miRNAs in the sequencing set, and potential miRNAs from independent samples in both the screening and validation sets were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Receiver operating characteristic (ROC) analysis was used to evaluate the ability of certain miRNAs to distinguish POAG patients from control subjects. RESULTS. Using sequencing and qRT-PCR, hsa-miR-210-3p was found to be elevated in POAG patients in all sets. ROC analysis of the screening and validation sets revealed that hsa-miR- 210-3p differentiated between POAG patients and matched controls with an area under the curve (AUC) of 0.846 (sensitivity: 84.6%; specificity: 80.8%) and 0.813 (sensitivity: 84.8%; specificity: 69.7%), respectively. In case of all nonsequencing participants, analysis revealed that hsa-miR-210-3p differentiated between severe POAG patients and controls with an AUC of 0.880 (sensitivity: 85.4%; specificity: 85.7%). In addition, the expression of hsa-miR-210-3p was associated with visual field defects of |mean deviation| (β = 0.237; P = 0.022) and average retinal nerve fiber layer thickness (β = -5.792; P = 0.014). CONCLUSIONS. Circulating hsa-miR-210-3p may serve as a potential diagnostic marker for POAG (especially for severe POAG patients).