Profiles of circulating exosomal miRNA in SAPHO patients by high-throughput sequencing

Abstract Background: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare disease characterized by autoinflammatory lesions on bones and skin. Diversified manifestation and inadequate understanding of etiology have limited its diagnosis and treatment. SAPHO syndrome is also classified as primary inflammatory osteitis. The osteoarticular involvement is generally insidious in onset of this disease and associated biomarkers may be of significance for diagnosis, treatment, as well as clarifying the pathogenesis of SAPHO. In this study, we profiled the exosomal miRNA expression in peripheral blood of SAPHO patients to identify key miRNAs associated with this disease and try to find new molecule as potential biomarkers for SAPHO syndrome. Methods: We recruited 6 SAPHO patients and 3 healthy volunteers. The expression profile of miRNAs in circulating exosome was analyzed by next generation sequencing. Linear discriminant analysis effect size analysis and Wilcoxon rank-sum test were used to screen the biomarker based on the differential miRNAs, and the receiver operating characteristic curve was constructed to assess the diagnostic value. We performed Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses to predict their potential functions and related pathways according to the target genes of the differential miRNAs. Results: In total 45 differentially expressed miRNAs in SAPHO patients were identified, among which 22 were upregulated and 23 were downregulated. MiR-144-3p was the most significantly upregulated miRNA. Meanwhile, miR-30d-3p, miR-627-3p, miR-556-5p, miR-18a-5p, miR-2355-3p, miR-24-1-5p, miR-6734-5p, miR-548d-5p, miR-548o-3p, miR-185-3p were distinctly expressed in SAPHO patients and undetectable in healthy volunteers. We identified 4 differential miRNAs (hsa-miR-150-5p, hsa-miR-144-3p, hsa-miR-142-5p and hsa-miR-30d-3) as biomarkers for SAPHO syndrome and the area under the receiver operating characteristic curve was 1. The differential KEGG pathways enriched in immune system and endocrine system, as well as the infectious disease and cancers; while most significantly indicated molecular function in GO function were protein binding and catalytic activity. Conclusion: The exosomal miRNA profile in SAPHO syndrome was significantly changed and could be treated as biomarker to assist the diagnose, while their parts in pathology needed further exploration in the future.