Hypothesis / aims of study
Interstitial cystitis and bladder pain syndrome lack reliable objective diagnostic biomarkers, resulting in variability in diagnosis and delayed treatment. We hypothesized that urinary extracellular vesicle derived microRNA profiles could serve as a novel, non-invasive biomarker for accurate detection of interstitial cystitis and bladder pain syndrome. The aim of this study was to comprehensively evaluate urinary extracellular vesicle microRNA expression and assess its diagnostic performance in patients with interstitial cystitis and bladder pain syndrome.
Study design, materials and methods
Urinary samples were collected from 20 individuals, including 8 patients with Hunner type interstitial cystitis, 2 patients with bladder pain syndrome, and 10 non-cystitis controls. All patients were clinically diagnosed using cystoscopy and standard criteria, and urinary tract infection was excluded. Extracellular vesicle microRNA was isolated from urine using a nanowire-based device, followed by comprehensive profiling using a microarray platform covering 2632 human microRNAs. After quality control, 485 microRNAs were included in the analysis. Leave one out cross validation and receiver operating characteristic analysis were performed to identify candidate biomarkers. MicroRNAs with an area under the curve of at least 0.85 and cross validated accuracy of at least 0.85 were selected. Correlations with clinical symptom scores were also evaluated.
Results
Principal component analysis and hierarchical clustering demonstrated partial separation between interstitial cystitis or bladder pain syndrome patients and controls (Figure 1A, B). Among the identified candidates, miR-373-5p and miR-6766-5p showed the highest diagnostic performance (Figure 1C). miR-373-5p demonstrated an area under the curve of 0.89 with a cross validated accuracy of 0.90, while miR-6766-5p showed an area under the curve of 0.86 with a cross validated accuracy of 0.85. Sensitivity and specificity values were approximately 0.90 and 0.80 to 0.90, respectively (Figure 2A). Expression of miR-6766-5p was significantly increased, while miR-373-5p was decreased in patients compared to controls (Figure 2B, C). No significant correlation was observed between microRNA levels and symptom severity scores.
Interpretation of results
This study demonstrates that urinary extracellular vesicle derived microRNA profiling can distinguish interstitial cystitis and bladder pain syndrome patients from controls with high diagnostic accuracy. The identified microRNAs may reflect underlying disease biology and represent a promising liquid biopsy approach. However, the small sample size, single center design, and lack of functional validation limit the generalizability of the findings.