Circulating microRNA-15b-5p as a biomarker for asthma-COPD overlap

Abstract

Background: It remains unclear how to characterize different subtypes of asthma and chronic obstructive pulmonary disease (COPD). We previously described serum periostin and chitinase-3-like protein 1 (YKL-40) as useful markers for asthma-COPD overlap (ACO). MicroRNAs (miRNAs) are now recognized as markers for identifying the pathophysiological features in several diseases. This study aimed to identify circulating miRNAs that could discriminate patients with ACO from patients with asthma or COPD.

Methods: This study included two independent cohorts. First, we screened 84 miRNAs for expression levels in patients with ACO (n = 6) or asthma (n = 6) using a quantitative real-time PCR array. The miRNAs showing at least a 2-fold difference in the discovery phase were analyzed in 30 patients each with asthma, COPD, or ACO in the replication phase. The diagnostic accuracy was evaluated using the area under the receiver operating characteristic curve (AUROC).

Results: Nine miRNAs were identified in the discovery phase. Five of these miRNAs (miR-148a-3p, miR-15b-5p, miR-223-3p, miR-23a-3p, and miR-26b-5p) had lower levels in ACO patients and could discriminate between ACO patients and patients with either asthma or COPD. miR-15b-5p was the most accurate miRNA for the discrimination of patients with ACO (AUROC, 0.71). Moreover, the combined assessment of miR-15b-5p, serum periostin, and YKL-40 (AUROC, 0.80) improved diagnostic accuracy for ACO compared with the combined model of periostin and YKL-40 (AUROC, 0.69).

Conclusions: Circulating miR-15b-5p is a potential marker for identifying patients with ACO. By elucidating the molecular pathways controlled by miRNAs, we may better understand the pathophysiology of ACO.

Keywords: asthma; asthma-COPD overlap; chronic obstructive pulmonary disease; miR-15b-5p; microRNA.