Evaluation of the diagnostic performance of circulating microRNAs for the diagnosis of autism spectrum disorders

Abstract

Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder with genetic and environmental influences. Recently, microRNA (miRNA), has been identified as a potential contributor to the pathogenesis of several neurodevelopmental abnormalities, including ASD. Aim This study aimed to assess the diagnostic performance of a miRNA panel (miR-146a-5p, miR-106b-5p, miR-148a-5p) in ASD diagnosis. Patients and methods Fifty children, 16 with ASD and 34 normally developing were enrolled in the study. Relative expression levels of plasma miR-146a-5p, miR-106b-5p, and miR-148a were determined by real-time reverse transcription-quantitative PCR. Receiver operator characteristic analysis was done to evaluate the diagnostic performance of the studied panel. Functional enrichment analysis was conducted to detect the relationship between miRNA targets and relevant pathways. Results Results showed significantly higher levels of all three miRNAs in ASD children compared to controls. Receiver operator characteristic analysis indicated high diagnostic accuracy for miR-106b-5p area under a curve (AUC)=0.959], miR-146a-5p (AUC=0.980), and miR-148a-5p (AUC=0.995). Functional analysis revealed enrichment of miRNA targets in pathways related to neurodevelopment, such as FoxO, PI3K-Akt, and HIF-1 signaling. MiR-146a-5p targets were enriched in innate immunity pathways like Toll-like receptor and chemokine signaling. These findings suggest a complex interplay between neuroepigenetics and neurogenetic pathways in ASD pathogenesis. Conclusion The proposed miRNA panel shows promise for distinguishing children with ASD from normally developing children. Moreover, the study highlights the intricate relationship between miRNAs and ASD-related pathways, emphasizing the need for further large-scale validation studies. Integrating genetic, epigenetic, and environmental factors may improve our understanding and management of ASD.