Serum exosomal miR-1258: A novel biomarker for the diagnosis of acute exacerbations of COPD

Abstract BACKGROUNDAcute exacerbation chronic obstructive pulmonary disease (AECOPD) has a high mortality rate, rapid identification of AECOPD from COPD is critical for timely treatment and improved prognosis. However, there is no efficiency biomarker for diagnosing AECOPD. OBJECTIVEThe purpose of this study was to find biomarkers that can quickly and accurately diagnose AECOPD and establish an effective laboratory diagnostic strategy.METHODS45 normal controls (NC), 42 patients with stable COPD (SCOPD), and 66 patients with AECOPD were enrolled in our study. Exosomes were isolated by ultracentrifuge and verified by morphology and specific biomarkers. Fluorescent quantitation polymerase chain reaction (qRT-PCR) was used to detect the expression of micro RNAs (miRNAs) in serum and exosomes. We constructed the diagnostic models of AECOPD using logistic regression and machine learning methods. RESULTSThe levels of miR-1258 in the patients with AECOPD were higher than that in the patients with COPD and NC both in serum and exosomes. The ability of exosomal miR-1258 (AUC=0.851) to identify AECOPD from SCOPD was superior to neutrophil to lymphocyte ratio (NLR) (AUC=0.797), serum miR-1258 (AUC=0.790), neutrophil count (AUC=0.727), white blood cell count (WBC) (AUC=0.654) and C-reactive protein (CRP) (AUC=0.635), and the combination of exosomal miR-1258 and NLR can increase the AUC to 0.944, with a sensitivity of 81.82%, and specificity of 97.62%. The cross-validation of the models displayed that the logistic regression model based on exosomal miR-1258, NLR and neutrophil count had the best accuracy (0.880) in diagnosing AECOPD from SCOPD. Training set for decision tree showed that of the 108 patients with SCOPD and AECOPD, 50 patients with miR-1258 greater than 0.197, 49 of them had a neutrophil greater than 2.705x10 9 /L were diagnosed with AECOPD. Serum exosome miR-1258 was positively correlated with neutrophil count (r=0.57, p<0.001), WBC (r=0.50, p<0.001), CRP (r=0.33, p<0.001), lactic dehydrogenase (LDH) (r=0.29, p<0.001), and NLR (r=0.24, p<0.05).CONCLUSIONSerum exosomal miR-1258 is associated with inflammation, and can be used as a valuable and reliable biomarker for the diagnosis of AECOPD, and the establishment of diagnostic model based on miR-1258, NLR and neutrophils can help improve the accuracy of AECOPD diagnosis. Serum exosomal miR-1258 for AECOPD