Prostate cancer (PCa) is one of the leading causes of cancer death in men. While prostate-specific antigen (PSA) testing is widely used for screening, its diagnostic accuracy is limited, often failing to distinguish between benign and malignant prostate conditions, underscoring the need for novel biomarkers with improved diagnostic performance.
This study aimed to identify and validate a panel of urinary RNA biomarkers with improved diagnostic accuracy for PCa.
RNA-sequencing analysis of exfoliated cells in urine specimens identified 50 candidate RNAs. After initial qPCR testing in pooled urine, three biomarkers (TTC3, H4C5, EPCAM) with optimal specificity and sensitivity were selected as a biomarker panel. Diagnostic performance was evaluated in a case-control study divided into development (n = 243 participants) and validation (n = 646 participants) datasets. Biomarker expression was confirmed in tissue specimens, and the oncogenic function of TTC3 was assessed in vitro and in vivo.
The three-biomarker urine panel robustly identified PCa with an area under the curve (AUC) of 0.96 (95% CI: 0.94-0.98) compared to 0.83 (95% CI: 0.77-0.88) for urinary prostate cancer antigen 3 (PCA3) RNA in the development dataset and 0.92 (95% CI: 0.89-0.94) compared to 0.76 (95% CI: 0.72-0.80) for PCA3 in the validation dataset. Urine biomarkers were nearly eliminated post-prostatectomy and were confirmed to originate from prostate tissue at both the RNA and protein levels. The panel maintained high diagnostic accuracy of PSA-negative PCa cases and distinguished PCa from benign prostate conditions (BPH, prostatitis). Functional studies demonstrated that TTC3 depletion significantly suppressed in vitro and in vivo tumour growth.
This urine-based biomarker panel offers a promising sensitive and specific noninvasive diagnostic for PCa with the potential to form the basis for laboratory-developed and in vitro diagnostic assays.
This study was supported by the International Prostate Cancer Foundation, JHU SKCCC (grant number P30CA006973), and Bankhead-Coley Cancer Research Program (grant number 24B16) to R. J. Perera and by the Maryland Innovation Initiative Grant to C. P. Pavlovich and R. J. Perera.
EBioMedicine. 2025 Aug 23 [Epub ahead of print]
Menglang Yuan, Marcio Covas Moschovas, Kandarp Joshi, Yohei Sanada, Roshane A Perera, Bongyong Lee, Rudramani Pokhrel, Jiri Polivka, Alexandra Miller, Ernest K Amankwah, Ignacio Gonzalez-Gomez, Naren Nimmagadda, Ezra Baraban, Anant Jaiswal, Cuncong Zhong, Inoel Rivera, Guru P Sonpavde, Chetan Bettegowda, Vipul Patel, Christian P Pavlovich, Ranjan J Perera
Department of Neurosurgery and Oncology, Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, 1650 Orleans St., Baltimore, MD, 21231, USA; Johns Hopkins All Children's Hospital, 600 5th St. South, St. Petersburg, FL, 33701, USA., AdventHealth Global Robotics Institute, 380 Celebration Place, Celebration, FL, 34747., Department of Histology and Embryology and Biomedical Center, Faculty of Medicine in Plzen, Charles University, Prague, Czech Republic., Johns Hopkins All Children's Hospital, 600 5th St. South, St. Petersburg, FL, 33701, USA., The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, 600 N Wolfe St., Baltimore, MD, 21287, USA., Department of Pathology, Johns Hopkins University School of Medicine, 1800 Orleans St., Baltimore, MD, 21287, USA., Department of Electrical Engineering and Computer Science, University of Kansas, 1520 W 15th St., Lawrence, KS, 66045, USA., Orlando Health Medical Group Urology-Winter Park, 303 E Par St., Orlando, FL, 32804, USA., AdventHealth Cancer Institute, 2501 N Orange Ave, Orlando, FL, 32804, USA., Department of Neurosurgery and Oncology, Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, 1650 Orleans St., Baltimore, MD, 21231, USA., Department of Neurosurgery and Oncology, Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, 1650 Orleans St., Baltimore, MD, 21231, USA; Johns Hopkins All Children's Hospital, 600 5th St. South, St. Petersburg, FL, 33701, USA. Electronic address: .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/40903311