cfDNA Fragmentation Patterns Show Promise to Detect and Stage Bladder Cancer

A study published in The Journal of Molecular Diagnostics demonstrates that analyzing cell-free DNA (cfDNA) fragmentation patterns in urine can effectively diagnose and stage bladder cancer, offering a less invasive option than cystoscopy. This approach could help reduce patient discomfort, healthcare costs, and dependence on frequent cystoscopic procedures.

Bladder cancer remains one of the most common and lethal urological cancers, marked by a high recurrence rate and reliance on invasive diagnostic techniques. Standard diagnosis often involves cystoscopy, where a thin tube is inserted through the urethra to visualize the bladder, or urine cytology, which can identify tumor cells but lacks sensitivity. The new study explores whether cfDNA fragmentation signatures in urine could serve as a simpler and more reliable alternative.

The research team from Health Research Institute Hospital La Fe analyzed urine samples from 156 patients with bladder cancer and 79 matched controls. Using real-time PCR, they measured both the concentration and size distribution of cfDNA fragments from five genes: ACTB, AR, MYC, BCAS1, and STOX1. Comparing fragment integrity across samples allowed them to identify patterns associated with disease presence and stage.

“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,” said lead investigator Pilar Medina. MYC encodes a transcription factor essential for cell growth, proliferation, and metabolism.

The study further showed that the ratio of large to small fragments of the housekeeping gene ACTB and the small fragment of the AR gene rose with disease severity, making them promising biomarkers for staging. Differences in gene integrity could also help detect relapse.

“With growing interest in liquid biopsies and personalized medicine, our study offers a timely and practical alternative to invasive diagnostics,” said lead author Raquel Herranz. “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.”