Serum exosomal miR-328, miR-575, miR-134 and miR-671-5p as potential biomarkers for the diagnosis of Kawasaki disease and the prediction of therapeutic outcomes of intravenous immunoglobulin therapy

摘要

The present study was conducted to screen serum exosomal microRNAs (miRNAs) for the early diagnosis of Kawasaki disease (KD) and to investigate their underlying mechanisms by analyzing microarray data under accession numbers GSE60965 [exosomal miRNA, including three pooled serum samples from 5 healthy children, 5 patients with KD and 5 patients with KD following intravenous immunoglobulin (IVIG) therapy] and GSE73577 (mRNA, including peripheral blood mononuclear cell samples from 19 patients with KD prior to and following IVIG treatment) from the Gene Expression Omnibus database. Differentially expressed miRNAs (DE-miRNAs) and genes (DEGs) were identified using the Linear Models for Microarray data method, and the mRNA targets of DE-miRNAs were predicted using the miRWalk 2.0 database. The functions of the target genes were analyzed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). As a result, 65 DE-miRNAs were identified with different expression patterns between the healthy children and patients with KD and between patients with KD and patients with KD following IVIG therapy. The target genes of 15 common DE-miRNAs were predicted. Following overlapping the target genes of DE-miRNAs with 355 DEGs, 28 common genes were identified and further screened to construct a network containing 30 miRNA-mRNA regulatory associations. Of these associations, only miR-328-spectrin , erythrocytic 1, miR-575-cyclic AMP-responsive element-binding protein 5/b-1,4-galactosyltransferase 5/WD repeat and FYVE domain-containing 3/cystatin-A/C-X-C motif chemokine receptor 1/protein phosphatase 1 regulatory subunit 3B, miR-134-acyl-CoA synthetase long chain family member 1/C-type lectin domain family 1 member A and miR-671-5p-tripartite motif containing 25/leucine rich repeat kinase 2/kinesin family member 1B/leucine rich repeat neuronal 1 were involved in the negative regulation of gene expression. Functional analysis indicated that the identified target genes may be associated with inflammation. Accordingly, serum exosomal miR-328, miR-575, miR-134 and miR-671-5p may act as potential biomarkers for the diagnosis of KD and the prediction of outcomes of the IVIG therapy by influencing the expression of inflammatory genes.