Urinary exosomal miRNA profiling reveals sensitive non-invasive detection of bladder cancer

BACKGROUND: Urinary microRNAs (miRNAs) hold substantial promise as non-invasive biomarker candidates due to their molecular stability and tumor-selective expression signatures. This study integrates the high-throughput urinary miRNA landscape with clinical data to systematically identify robust, non-invasive biomarkers that facilitate the early diagnosis and better clinical management of urinary bladder cancer (UBC). METHODS: Urine-derived miRNA sequencing was performed on UBC patients and healthy controls to delineate the miRNA expression profile. Computational filtering further excluded precursor form of miRNA, prioritizing the mature miRNA. Quantitative RT-PCR targeting an independent, age-matched cohort (n = 48) corroborated with the diagnostic potential of candidate miRNAs, evaluated through receiver operating characteristic (ROC) curves and area under the curve (AUC) analyses. RESULTS AND LIMITATIONS: Next-generation sequencing unveiled 865 annotated and 11 novel miRNAs, with UBC samples displaying greater miRNA diversity (708 known miRNAs) compared to relative controls (540). Among them, seven mature miRNAs were significantly dysregulated in UBC (p < 0.05), of which quantitative RT-PCR corroborated significant upregulation of miR-6724-5p, miR-1273 h-5p, miR-7704, miR-200-5p, and miR-10400-5p, with fold elevations of 1542.3, 1085.8, 1160.6, 2776.5, and 45.8, respectively (p < 0.01). Stage-stratified profiling underscored dynamic shifts in miRNA expression that correlated with tumor advancement. A three-miRNA panel (miR-6724-5p, miR-10400-5p, and miR-7704) exhibited superior diagnostic performance (AUC > 70%, sensitivity > 90%). However, this study was constrained to a single institute with a small sample size and a short follow-up period, which precluded the correlation between the identified biomarker miRNAs with cancer recurrence and patient survival. CONCLUSION: In this preliminary, single-centre study, mature urinary miRNAs demonstrated reproducible, stage-specific dysregulation in UBC. A combinatorial panel offered potential for a highly sensitive, specific, and non-invasive detection method. These findings propel further multicentre studies to validate the observed signatures, supporting their potential towards future clinical application.