Serum exosomal long noncoding RNAs as a diagnostic biomarker for atrial fibrillation

Abstract

BACKGROUND Exosomal long noncoding RNAs (lncRNAs) are known as ideal diagnostic biomarkers of various diseases. However, there are no reports on the use of serum exosomal lncRNAs as diagnostic biomarkers for atrial fibrillation (AF). OBJECTIVE The purpose of this study was to explore serum exosomal lncRNAs as a useful tool for diagnosing AF. METHODS Serum exosomes from patients with persistent AF and controls were isolated using a polymer-based exosome precipitation kit. We conducted a multiphase process including screening and 2 independent validation phases. In the screening phase, serum exosomal lncRNA expression profiles were examined using RNA sequencing analysis. In 2 validation phases, we evaluated the expression levels of candidate exosomal lncRNAs using quantitative reverse transcription polymerase chain reaction. Finally, we performed different statistical and functional analyses. RESULTS After the screening phase, we identified 26 differentially expressed lncRNAs (ie, 15 upregulated and 11 downregulated lncRNAs with a vertical bar fold change vertical bar >= 2 and P<.05) in serum exosomes from patients with persistent AF compared with controls. We then screened out 6 exosomal lncRNAs as biomarker candidates following parameters: read length >= 200 nucleotides; exon number >= 2; and coding potential score <0.1. In 2 validation phases, exosomal lncRNAs LOC105377989 and LOC107986997 were consistently upregulated in the serum of patients with persistent AF compared with controls (P<.0001). Moreover, both exosomal lncRNAs exhibited significant diagnostic validity for AF. Notably, exosomal lncRNA LOC107986997 was involved in AF-related pathophysiological mechanisms. CONCLUSION Serum-derived exosomal lncRNA LOC107986997 could serve as a potential biomarker for AF diagnosis.