Urinary microRNA Dysregulation Discriminates Prostate Cancer from Benign Prostatic Hyperplasia: A Two-Phase Small-RNA Sequencing Study

Urinary microRNAs (miRNAs) may help distinguish prostate cancer (PCa) from benign prostatic hyperplasia (BPH). We assessed reproducibility across two independently re-cruited and sequenced cohorts: an exploratory cohort of seven subjects (3 PCa, 4 BPH) and an expanded cohort of 25 (13 PCa, 12 BPH). Cross-cohort comparisons included only mature miRNA identifiers present in both analysis tables. Among 177 shared miRNAs, log2 fold changes correlated (Pearson r=0.79; Spearman rho=0.70), and 76.3% agreed in direction. Twenty-seven miRNAs met differential-expression thresholds in both cohorts with concordant direction, including down-regulated immune-associated miRNAs and up-regulated epithelial-associated candidates. Seven of the ten highest-ranked explor-atory candidates were available in both tables and formed a direction-weighted com-posite score. Its area under the receiver operating characteristic curve (AUC) was 0.897 in the expanded cohort. In 14 subjects with serum prostate-specific antigen (PSA), panel and PSA AUCs were 0.875 and 0.500, respectively (paired difference 0.375; 95% bootstrap interval −0.062 to 0.771). No association with PSA was detected (Spearman rho=−0.15). BPH showed heterogeneous expression, including a PCa-like subset. These exploratory findings support further evaluation of urinary miRNAs; larger prospective studies and orthogonal assays are required to establish clinical utility.