Role of urinary exosomal FAM153C-RPL19 in detection and risk stratification of prostate cancer: A multicentre Chinese cohort study.

Abstract

374 Background: Serum PSA lacks specificity for prostate cancer (PCa), especially within the 4–10 ng/mL “grey zone,” leading to unnecessary biopsies and missed high-grade disease. Urinary exosomes concentrate tumour-derived RNAs and may improve non-invasive diagnosis. We evaluated a chimeric RNA, FAM153C-RPL19, in urinary exosomes as a diagnostic and prognostic marker for PCa.To determine the clinical performance of urinary exosomal FAM153C-RPL19 for PCa detection (overall and PSA grey zone), compare it with PSA and PCA3, test multi-marker models, and assess associations with grade, stage and progression-free survival (PFS). Methods: We analysed tissue, plasma and urine across three centres (Nanfang Hospital, Sun Yat-sen Memorial Hospital, Peking University People’s Hospital). Discovery used CPGEA and external validation cohorts; urinary/plasma exosomes were isolated by standardised SOPs (sequential centrifugation→TFF→ultracentrifugation). FAM153C-RPL19 was quantified by RT-qPCR with rigorous assay QC. Diagnostic performance was assessed by ROC/AUC; multivariable Cox tested prognostic value for PFS; multiple testing used Bonferroni/FDR where appropriate. Pre-specified subgroup analyses included PSA grey zone and Gleason/Stage strata. Results: Among 2,002 participants (PCa = 826; BPH = 396; non-PCa cancers = 352; healthy = 428), urinary exosomal FAM153C-RPL19 was significantly elevated in PCa versus all control groups and increased with higher Gleason score (≥7) and advanced stage (III–IV). Urine outperformed plasma for the same individuals. Diagnostic accuracy was high (AUC = 0.93) and remained robust in PSA grey-zone patients (AUC = 0.92); FAM153C-RPL19 outperformed PSA (AUC = 0.81) and PCA3 (AUC = 0.75). A combined model (FAM153C-RPL19 + PSA + PCA3) achieved AUC = 0.97, supporting multiplex testing. Prognostically, higher urinary exosomal FAM153C-RPL19 predicted shorter PFS (HR = 2.95, 95% CI 1.90–4.58). Findings were consistent across centres with harmonised pre-analytics. Conclusions: Urinary exosomal FAM153C-RPL19 provides accurate, non-invasive detection of PCa and clinically meaningful risk stratification, particularly within the PSA grey zone, and could reduce unnecessary biopsies. Incorporation into multi-marker urine assays further boosts performance and supports translation toward point-of-care liquid biopsy pathways. Prospective studies should evaluate its impact on biopsy decision-making and surveillance algorithms.