A groundbreaking advancement in prostate cancer diagnostics emerges from the collaborative efforts of researchers at Johns Hopkins Kimmel Cancer Center, Johns Hopkins All Children’s Hospital, and four additional institutions. This pioneering study unveils a novel, noninvasive urine-based test that can accurately identify prostate cancer through a select panel of three biomarkers. The implications of this discovery extend far beyond traditional prostate-specific antigen (PSA) testing, offering a promising alternative that could drastically reduce the reliance on invasive biopsies, which are often painful and carry potential complications.
Historically, the detection of prostate cancer has heavily depended on blood tests measuring PSA, a protein produced by both cancerous and noncancerous prostate tissues. Although PSA testing has been an essential tool in screening, its specificity is limited. Elevated PSA levels above 4.0 nanograms per milliliter often prompt urologists to recommend prostate biopsies, which involve extracting multiple tissue samples via needles. However, these biopsies can be negative or result in overtreatment of low-grade prostate cancers unlikely to progress aggressively. This gap in diagnostic precision has driven the need for more accurate, minimally invasive methods.
The team spearheaded by Dr. Ranjan Perera, director of the Center for RNA Biology at Johns Hopkins All Children’s Hospital, employed advanced molecular profiling techniques to analyze urine samples from prostate cancer patients before and after prostatectomy, as well as from healthy individuals. By meticulously isolating prostate cells shed in urine and conducting RNA sequencing alongside real-time quantitative polymerase chain reaction (qPCR), researchers narrowed down 815 prostate-specific genes to a critical trio: TTC3, H4C5, and EPCAM. These markers were robustly linked to the presence of prostate cancer, showing significant expression in pre-surgery urine samples and near absence following surgical removal of the prostate.
TTC3, or tetratricopeptide repeat domain 3, is particularly notable for its role in asymmetric cell division in cancerous cells, a process vital to tumor heterogeneity and progression. H4C5 refers to an H4 clustered histone variant, a protein influential in chromatin remodeling, which impacts gene expression regulation and genome stability within malignant cells. EPCAM, the epithelial cell adhesion molecule, is a surface glycoprotein commonly overexpressed in epithelial-derived cancers. The synergistic detection of these three biomarkers in urine offers a molecular fingerprint that is both highly sensitive and specific to prostate malignancies.
In comprehensive validation studies, the three-marker panel demonstrated an impressive area under the curve (AUC) of 0.92, indicating near-perfect diagnostic performance. The test accurately identified prostate cancer in 91% of cases and effectively ruled out non-cancerous individuals 84% of the time. Remarkably, it also distinguished prostate cancer patients from those with benign prostatic hyperplasia (BPH), a benign enlargement of the prostate that often confounds clinical diagnoses. This specificity extends even to patients whose PSA levels remain within normal ranges, addressing a critical diagnostic blind spot where current PSA tests falter.
The researchers did not stop at typical PSA-positive cases but intentionally investigated the panel’s effectiveness in PSA-negative prostate cancers. Even within this challenging subset, the test retained high diagnostic accuracy, correctly identifying malignancies in 78.6% of cases during development and 85.7% during validation. Such sensitivity could transform early detection protocols for men who otherwise might be overlooked by PSA screening. Furthermore, this assay showed the ability to differentiate prostate cancer from prostatitis, an inflammatory prostate disease that can also obscure clinical assessments.
The methodology entailed extensive sample collection from multiple centers, capturing a diverse cross-section of patients and controls. In total, the study evaluated over 1,300 urine specimens across both development and validation phases, ensuring statistical robustness. The high-throughput analyses coupled with immunohistochemical studies on tissue biopsies correlated biomarker expression in urine with that observed directly in malignant prostate tissues. This multi-platform validation confirms that these biomarkers derive specifically from prostate cancer cells, reinforcing the biological relevance of the test.
Current prostate cancer diagnostic standards are burdened by the limitations of PSA screening – namely its lack of specificity and the invasive nature of follow-up biopsies. As Dr. Perera emphasizes, these biopsies carry risks such as infection and bleeding, and negative results occur frequently, leading to patient anxiety and increased healthcare costs. By introducing a sensitive, urine-based assay, patients could potentially avoid these invasive procedures altogether unless clearly indicated, optimizing both patient well-being and resource allocation.
Co-author Dr. Christian Pavlovich, a distinguished professor of Urologic Oncology, highlights the clinical practicality of urine as a diagnostic medium. Given that urine collection is noninvasive, inexpensive, and easy to implement in outpatient settings, the adoption of such a test could be swift and widespread, enhancing prostate cancer screening while reducing dependence on blood-based PSA measurements. The test’s ability to act as an adjunct or standalone diagnostic tool heralds a new era in precision urology.
Looking ahead, investigators are contemplating integrating the three-biomarker panel with PSA testing to create a “super PSA” assay, combining the strengths of both approaches to maximize diagnostic accuracy. Clinical trials at independent institutions are planned to further validate the assay’s performance, with the ultimate goal of transitioning this discovery from research laboratories into clinical practice. Efforts are also underway to patent the technology and explore commercial development opportunities through technology transfer and startup formation.
The research, supported by several funding agencies including the National Institutes of Health, the Bankhead-Coley Cancer Research Program, and the International Prostate Cancer Foundation, signifies a major leap forward in biomarkers for urologic oncology. As this panel advances through clinical validation and regulatory review, it promises to redefine prostate cancer diagnosis, improving patient outcomes through earlier intervention and reducing the emotional and physical toll of unnecessary procedures.
In conclusion, this innovative urine test targeting TTC3, H4C5, and EPCAM biomarkers marks a transformative step towards precision medicine in prostate cancer. With its superior sensitivity, specificity, and noninvasive nature, it addresses critical limitations in current screening paradigms and paves the way for personalized diagnostic strategies. This scientific milestone reflects a multidisciplinary triumph, blending molecular biology, clinical oncology, and cutting-edge technology to confront one of the most prevalent malignancies affecting men worldwide.
Subject of Research: Prostate cancer diagnosis using urine biomarkers
Article Title: Novel Urine Biomarker Panel Demonstrates High Accuracy for Noninvasive Prostate Cancer Detection
News Publication Date: September 2, 2025
Web References: Johns Hopkins Kimmel Cancer Center (https://www.hopkinsmedicine.org/kimmel_cancer_center/), Johns Hopkins All Children’s Hospital (https://www.hopkinsmedicine.org/all-childrens-hospital)
References: Published in EBioMedicine on September 2, 2025
Image Credits: Johns Hopkins All Children’s Hospital
Keywords: Prostate cancer, biomarkers, TTC3, H4C5, EPCAM, urine test, noninvasive diagnostics, PSA, biopsy alternative
