Plasma exosomal miRNA sequencing of COPD

Exosomal microRNAs (exo-miRNAs or miRs) have demonstrated diagnostic value in various diseases. However, their diagnostic value in chronic obstructive pulmonary disease (COPD) is yet to be established. The purpose of the current study was to screen differentially expressed exo-miRNAs in the plasma of patients with COPD and healthy controls, and evaluate their diagnostic value in COPD. The differentially expressed exo-miRNAs in the plasma of patients with COPD and controls were identified using high-throughput sequencing and confirmed via reverse transcription-quantitative PCR (RT-qPCR). Bioinformatics analysis was performed to predict the function of exo-miRNA and their target genes in COPD. After a network model was constructed, linear regression analysis was performed to determine the association between exo-miRNA expression and the clinical characteristics of patients in a validated cohort. A receiver operating characteristic curve was subsequently plotted to test the diagnostic value of candidate biomarkers. The top 20 significantly aberrantly expressed COPD-associated exo-miRNAs were verified via RT-qPCR. Nine were then selected for subsequent analysis, five of which were upregulated (miR-23a, miR-1, miR-574, miR-152 and miR-221) and four of which were downregulated (miR-3158, miR-7706, miR-685 and miR-144). The results of Gene Ontology analysis revealed that these miRNAs were mainly involved in certain biological functions and signaling pathways associated with COPD. The expression levels of three exo-miRNAs (miR-23a, miR-221 and miR-574) were negatively associated with the forced expiratory volume in the 1st second/forced vital capacity. Furthermore, the area under the curve values of the three exo-miRNAs (miR-23a, miR-221 and miR-574) for COPD diagnosis were 0.776 [95% confidence interval (CI), 0.669-0.882], 0.688 (95% CI, 0.563-0.812) and 0.842 (95% CI, 0.752-0.931), respectively. In conclusion, the three circulating exosomal miRNAs (miR-23a, miR-221 and miR-574) may serve as novel circulating biomarkers for the diagnosis of COPD. The results may also provide new understanding and potential treatment options for patients with COPD.