Circular RNA expression alteration identifies a novel circulating biomarker in serum exosomal for detection of alcohol dependence.

Abstract

Alcohol dependence (AD) is one of the most common and detrimental neuropsychological disorders. Recently, more and more studies have focused on circular RNA as markers for central nervous system (CNS) diseases. The present study was conducted to evaluate the circular RNA expression alteration in serum exosomal and to identify a novel circulating biomarker for the detection of AD. We first isolated exosomes from serum and then investigated the circRNA expression alterations by high throughput whole transcriptome sequencing. The data were then analyzed using bioinformatics methods. Moreover, we verified the circRNA-seq by qRT-PCR. Furthermore, we analyzed the correlations between the levels of hsa_circ_0004771 and both Severity of Alcohol Dependence Questionnaire (SADQ) and Alcohol Dependence Scale (ADS). The diagnostic value of hsa_circ_0004771 in AD patients was evaluated by receiver operating characteristic (ROC). In this study, 254 differentially expressed circRNAs were identified, with 149 upregulated and 105 downregulated. GO analysis showed that these differentially expressed circRNAs from exosomes might be associated with the regulation of neuron projection and axon regeneration. KEGG analysis revealed that T cell receptor signaling and antigen processing and presentation pathway had a regulating effect on upstream levels. We found that hsa_circ_0004771 was related to the severity of AD. The AUC for the diagnostic value of hsa_circ_0004771 in AD patients was 0.874. These findings indicated that circRNA in serum exosomes provide novel targets for further research on molecular mechanisms of AD. Among these, hsa_circ_0004771 may be a sensitive biomarker that was related to the severity of AD.