Urine cfDNA patterns emerge as a promising tool for diagnosing bladder cancer

Researchers have discovered that analyzing specific patterns of cell-free DNA (cfDNA) fragmentation in a simple urine sample can effectively diagnose and stage bladder cancer, offering a much-needed alternative to invasive procedures like cystoscopies. This novel approach, detailed in a new study in The Journal of Molecular Diagnostics, published by Elsevier, could reduce the need for frequent cystoscopies, lower healthcare costs, and improve patient comfort and outcomes.

Bladder cancer remains a major clinical challenge as it is one of the most common and deadliest urological cancers with a high recurrence rate. Yet its diagnosis still relies heavily on invasive and costly procedures like cystoscopy (inserting a thin, tube-like instrument through the urethra) or cytology, a noninvasive test that can identify tumor cells shed in urine but has limited sensitivity.

Investigators of the current study were motivated to find a simpler, more comfortable way to detect and monitor bladder cancer. They analyzed urine samples from 156 patients with bladder cancer and 79 matched controls and using real-time PCR, measured the concentration and integrity (long-short size distribution) of cfDNA fragments from five genes (ACTB, AR, MYC, BCAS1, and STOX1).

"Our most significant finding was that the small fragment of the MYC gene may represent a valuable tool to diagnose bladder cancer, as it exhibited excellent specificity (97%) and predictive value (88%) for identifying muscle-invasive bladder cancer," explains lead investigator Pilar Medina, PhD, Haemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Health Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain.

MYC produces a transcription factor crucial for regulating cell growth, proliferation, and metabolism.

Additionally, researchers found that the ratio of large to small fragments of the housekeeping gene ACTB and the small fragment of the AR gene increased with disease severity, suggesting these could be reliable staging biomarkers. The integrity of these genes may be useful to identify bladder cancer relapse.

Lead author Raquel Herranz, MS, Haemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Health Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain, notes, "With growing interest in liquid biopsies and personalized medicine, our study offers a timely and practical alternative to invasive diagnostics. This study is one of the first to comprehensively evaluate urine cfDNA fragmentation and integrity across most bladder cancer stages, bringing us closer to a future in which bladder cancer can be diagnosed and monitored through a simple urine test, improving patient comfort and care."

Dr. Medina concludes, "Our findings show that urine can tell us much more than we thought; it holds the potential to transform how we detect and manage bladder cancer."