Researchers have developed a novel method to test for prostate cancer using biomarkers present in urine. This approach may significantly reduce the need for invasive, often painful biopsies, the researchers said in a statement. The study, which was funded in part by the National Institutes of Health (NIH) and conducted by senior study author Ranjan Perera, PhD, and colleagues, was published in eBioMedicine.1 Dr. Perera is Director of the Center for RNA Biology at Johns Hopkins All Children’s Hospital, St. Petersburg, Florida, and Professor of Oncology and Neurosurgery at the Johns Hopkins University School of Medicine.
Ranjan Perera, PhD
By analyzing urine samples from patients with prostate cancer before and after prostatectomy, as well as from healthy individuals, the study investigators identified a panel of three biomarkers that detected the presence of prostate cancer—TTC3 (tetratricopeptide repeat domain 3), H4C5 (H4 clustered histone 5), and EPCAM (epithelial cell adhesion molecule). These biomarkers were detectable in patients prior to surgery but were nearly absent after surgery. In brief, TTC3 plays a role in asymmetric cell division in cancer cells, H4C5 plays a role in modulating the structure of chromatin, and EPCAM is a protein highly overexpressed in many human cancers that originate in the epithelial tissue lining the surface of organs and structures throughout the body.
“This new biomarker panel offers a promising, sensitive and specific, noninvasive diagnostic test for prostate cancer,” stated Dr. Perera. “It has the potential to accurately detect prostate cancer, reduce unnecessary biopsies, improve diagnostic accuracy in PSA-negative patients, and serve as the foundation for both laboratory-developed and in vitro diagnostic assays.”
“There is a real need for non-PSA–based biomarkers for prostate cancer, and urine is quite easy to collect in the clinic,” added study coauthor Christian Pavlovich, MD, the Bernard L. Schwartz Distinguished Professor of Urologic Oncology at Johns Hopkins and Program Director for the Prostate Cancer Active Surveillance Program. “Most urologists feel that an accurate urinary biomarker would be a valuable addition to our current diagnostic armamentarium.”
Study Details
Investigators studied biomarkers in urine samples from healthy individuals as well as from patients with biopsy-proven prostate cancer undergoing prostatectomy at The Johns Hopkins Hospital, Johns Hopkins Bayview Medical Center, or AdventHealth Global Robotics Institute in Celebration, Florida. They studied 341 urine specimens (107 from healthy individuals, 136 from patients with prostate cancer before surgery, and 98 from patients after surgery). They also assessed an additional 1,055 specimens (162 from healthy individuals, 484 from patients with prostate cancer before surgery, and 409 from patients after surgery) to validate the test.
There is a real need for non–PSA-based biomarkers for prostate cancer, and urine is quite easy to collect in the clinic.— Christian Pavlovich, MD
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Investigators extracted RNA from prostate cells shed in 50-mL urine samples and analyzed them using RNA sequencing and also real-time quantitative polymerase chain reaction to study gene expression. In addition, they used immunohistochemistry to study biomarkers in samples from cancerous prostate tissue and healthy adjacent tissue as well as statistical analyses to compare biomarkers found in the urine and tissue samples.
Three-Biomarker Panel
Researchers tested the three-biomarker panel in a development group and a validation group. The test had an AUC of 0.92. The panel maintained diagnostic accuracy in 78.6% of the development group and 85.7% of the validation group of prostate-specific antigen (PSA)-negative prostate cancer cases. It also determined that the panel could distinguish patients with prostate cancer from benign prostate conditions with an AUC of 0.89.
Overall, expression levels of the three biomarkers were found to be significantly higher in urine samples from individuals with prostate cancers than in urine from the healthy controls. The expression of each biomarker diminished to low or undetectable levels in samples taken after prostate surgery. A greater proportion of patients with prostate cancer tested positive for the three biomarkers than for prostate cancer antigen 3, another biomarker associated with prostate cancers, in both the development and validation groups.
Investigators are considering how the biomarker panel may be used alone or combined with a PSA test to make a “super PSA,” commented Dr. Perera. The next steps are to have an independent trial of the test at another institution and to further develop the test for laboratory use in clinical settings, he noted.
DISCLOSURE: The work was supported by the International Prostate Cancer Foundation, the Johns Hopkins Kimmel Cancer Center (NIH grant # P30CA006973), the Bankhead-Coley Cancer Research Program (grant # 24B16) to Dr. Perera, and the Maryland Innovation Initiative Grant to Drs. Pavlovich and Perera. For full disclosures of all study authors, visit sciencedirect.com.
REFERENCE
1. Yuan M, Moschovas MC, Joshi K, et al: A sensitive and specific non-invasive urine biomarker panel for prostate cancer detection. eBioMedicine. September 2, 2025 (early release online).
