Novel urine-enriched RNA panel (EPCAM, TTC3, H4C5) to detect prostate cancer and differentiate it from benign prostatic disease.

• DOI: 10.1200/jco.2025.43.5_suppl.31
• Publication Date: 2025-02-18T14:32:56Z
• Authors: Ranjan Joseph Perera; Menglang Yuan; Marcio Moschovas; Roshane Perera; Ernest Amankwah; Bongyong Lee; Guru P. Sonpavde; Vipul Patel; Christian P. Pavl...; Kandarp Joshi
• Keywords: Prostatic Diseases

31 Background: Prostate Cancer (PCa) is one of the leading causes cancer deaths among men worldwide. Although Prostate-Specific Antigen (PSA) test widely used for screening, several advisory groups recommend against PSA because its non-specific and suboptimal performance. Hence, there an urgent unmet need novel more accurate biomarker panels PCa detection. Methods: To develop alternate assay, we collected voided urine (50 ml) from 236 pre- 198 matched post-prostatectomy with PCa, 76 benign prostatic hyperplasia (BPH), 21 prostatitis 107 normal healthy between years 40-80. We isolated RNA exfoliated cells debris shed into urine, subjected to deep-sequencing 50 selected genes (adj P value < 0.05 log FC > 2), performed advanced machine-learning approaches discover potential biomarkers in PCa. Results: From RNAs initially tested 20 pooled samples, 3 (EPCAM, TTC3, H4C5) were identified detect robustly (with higher specificity sensitivity) distinguished them patients. The biomarkers, combination, outperformed a known urinary marker, PCA3 (area under curve, 0.96, Figure 1 left). Immunohistochemistry qPCR analysis prostate FFPE tissues further confirmed that origin these three prostate-specific. In addition, panel could separate disease 0.89), where both diseases show elevation PSA. TTC3 EpCAM gene silencing showed tumor suppression vitro vivo , suggesting relevance development. Conclusions: urine-based promising noninvasive diagnostic tool BPH/prostatitis individuals; prospective validation warranted.