Prostate Cancer: New Urine Test Detects Key Biomarkers

by Grace Chen

Novel Urine Test Shows Promise for Early, Non-Invasive Prostate Cancer Detection

A groundbreaking new method for detecting prostate cancer using biomarkers found in urine could considerably reduce the need for painful and often needless biopsies, according to research published September 2 in eBioMedicine.

For men facing the possibility of prostate cancer, the current diagnostic pathway frequently enough begins with a prostate-specific antigen (PSA) blood test. Though, the PSA test’s limitations – its tendency to produce false positives – frequently lead to invasive biopsies, which carry risks of complications and can detect low-grade cancers that may never pose a threat. Now, a team of researchers from the Johns Hopkins Kimmel Cancer Center, Johns Hopkins All Children’s hospital, and four other institutions has developed a potentially game-changing choice.

The new approach centers on identifying a panel of three biomarkers – TTC3, H4C5, and EPCAM – present in urine samples. Researchers analyzed samples from patients before and after prostate removal surgery, as well as from healthy individuals, discovering that these biomarkers were consistently detectable in those with prostate cancer but nearly absent after surgical removal, confirming their origin in prostate tissue.

“This new biomarker panel offers a promising, sensitive and specific, noninvasive diagnostic test for prostate cancer,” explained ranjan Chattrabhuti, Ph.D., a professor of pathology at the Johns Hopkins University School of Medicine and co-senior author of the study. “It also effectively differentiated prostate cancer from other benign prostate conditions with an AUC of 0.89.

Understanding the Biomarkers

Each of the three biomarkers plays a distinct role in cancer development. TTC3 is involved in asymmetric cell division in cancer cells, H4C5 modulates chromatin structure (the complex of DNA and proteins within cells), and EPCAM is a protein frequently overexpressed in various human cancers originating in epithelial tissue.

Researchers extracted RNA from prostate cells shed in urine samples, analyzing gene expression using RNA sequencing and real-time quantitative polymerase chain reaction (qPCR). They also used immunohistochemistry to study biomarkers in tissue samples, comparing findings in urine and tissue. From an initial pool of 815 prostate-specific genes, the team meticulously narrowed down the selection to these three top performers.

A Non-Invasive Alternative

The potential benefits of this urine-based test extend beyond improved accuracy. As Christian Pavlovich, M.D., the Bernard L. Schwartz Distinguished Professor of Urologic Oncology at Johns Hopkins, noted, “There is a real need for non-PSA-based biomarkers for prostate cancer, and urine is quite easy to collect in the clinic.Most urologists feel that an accurate urinary biomarker would be a valuable addition to our current diagnostic armamentarium.”

The test’s ability to detect cancer even with normal PSA levels and differentiate it from conditions like prostatitis and BPH further underscores its potential. Vipul patel, M.D., director of urologic oncology at AdventHealth Cancer Institute, emphasized the broader impact: “This test has the potential to help physicians improve diagnostic accuracy of prostate cancer, reducing unnecessary interventions while allowing early treatment for those who need it.”

future Directions and Commercialization

The research team is now exploring the possibility of combining the biomarker panel with the PSA test to create a more extensive “super PSA.” Further steps include conducting an independent trial at another institution and developing the test for widespread clinical use. The investigators have filed a patent, and Johns Hopkins Technology ventures is assisting in the formation of a company to commercialize the technology.

The study involved analyzing 341 initial urine specimens and a subsequent validation set of 1,055 specimens collected from patients at The Johns Hopkins Hospital, Johns Hopkins Bayview Medical Center, and AdventHealth Global Robotics Institute. The research was supported by grants from the International Prostate Cancer Foundation,the National Institutes of Health,and the Maryland Innovation Initiative.

This innovative approach represents a notable step forward in prostate cancer diagnostics,offering the promise of earlier detection,reduced patient anxiety,and more informed treatment decisions.

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