Peripheral blood circMAN1A2 as a novel diagnostic biomarker for gout: integrated transcriptomic analysis and clinical validation.

BACKGROUND

Gout is one of the most common inflammatory arthritides. Although identification of monosodium urate crystals in synovial fluid is the diagnostic gold standard, the invasive procedure limits routine use. Non-invasive biomarkers are needed to facilitate timely diagnosis of acute gout flares and to differentiate gout from asymptomatic hyperuricaemia.

METHODS

Differential expression analysis was performed using the GEO circRNA microarray dataset GSE178825 (peripheral blood mononuclear cells, PBMCs; gout vs. healthy controls). Differentially expressed circRNAs were mapped to their host genes, followed by host-gene-based functional enrichment and protein-protein interaction (PPI) network analyses for candidate prioritization, circMAN1A2, derived from the MAN1A2 locus, was selected for clinical validation. PBMCs were isolated from whole blood samples obtained from 30 patients with acute gout flare, 30 individuals with HUA, and 30 healthy controls. Circularity was confirmed by RNase R resistance, and circMAN1A2 expression was quantified by RT-qPCR. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis.

RESULTS

Peripheral blood circMAN1A2 levels were significantly lower in patients with gout than in healthy controls, and showed a decreasing trend compared with individuals with HUA. circMAN1A2 showed preliminary diagnostic potential for gout (AUC = 0.86; 95% CI 0.66-1.00), with 90.0% sensitivity and 90.1% specificity.

CONCLUSION

Peripheral blood circMAN1A2 is a promising candidate biomarker for gout diagnosis. Integrating public transcriptomic mining with targeted clinical validation may accelerate biomarker discovery for gout.