Urinary Cell-Free DNA in Bladder Cancer Detection

Abstract

Urinary bladder cancer is a common urological cancer. Although flexible cystoscopy is widely employed in bladder cancer detection, it is expensive, invasive, and uncomfortable to the patients. Recently, urinary cell-free DNA (ucfDNA) isolated from urine supernatant has been shown to have great potential in bladder cancer detection and surveillance. Molecular features, such as integrity and concentration of ucfDNA, have been shown to be useful for differentiating bladder cancer patients from healthy controls. Besides, bladder cancer also exhibits unique genetic features that can be identified from sequencing and expression of ucfDNA. Apart from bladder cancer detection, ucfDNA is also useful for molecular classification. For example, ucfDNA exhibits significant differences, both molecularly and genetically, in non-muscle-invasive and muscle-invasive bladder cancers. There is no doubt that ucfDNA is a very promising tool for future applications in the field of bladder cancer.

Urinary Markers for Bladder Cancer Diagnosis and Monitoring

“…Thus, urine creatinine-adjusted DNA concentrations can be used for normalization. Notably, urine cfDNA of 400-bp was much more abundant than that of the control, whereas the median concentration was only higher by 1.5 fold in bladder cancers ( Tse et al, 2021 ). Additionally, a urine cfDNA concentration over 250 ng/ml was indicated as the threshold value to predict bladder cancers ( Tse et al, 2021 ).…”

“…Notably, urine cfDNA of 400-bp was much more abundant than that of the control, whereas the median concentration was only higher by 1.5 fold in bladder cancers ( Tse et al, 2021 ). Additionally, a urine cfDNA concentration over 250 ng/ml was indicated as the threshold value to predict bladder cancers ( Tse et al, 2021 ). Urine cfDNA sequencing has revealed valuable genetic mutations for the detection of bladder cancer.…”

“…The integrity of urine cfDNA is much higher in bladder cancer than under normal conditions ( Brisuda et al, 2016 ). Furthermore, the length of DNA fragments is relatively longer in bladder cancer, implying that it originates from the necrotic debris of cancer cells ( Tse et al, 2021 ). Urine cfDNA tests can detect bladder cancer with a sensitivity of 57–86% and specificity of 72–84% ( Salvi et al, 2016 ).…”

“…Urine cell-free DNA (cfDNA) originates from several sources, including urothelial cells, transrenal circulating DNA, and bacteria ( Tse et al, 2021 ). The majority of urine cfDNAs is from urothelial cells lining the urinary tract, which can be shed off and undergo necrosis or apoptosis to release DNA from the cells.…”

Serum EZH2 is a novel biomarker for bladder cancer diagnosis and prognosis

“…The early detection and continuous monitoring of bladder cancer have consistently presented challenges in the field of urology, largely due to the lack of highly sensitive and specific methods ( 10 , 11 ). Although cystoscopy is widely utilized as the gold standard for identifying bladder cancer, it is not a viable screening method owing to its invasive nature and high cost ( 12 ). At present, urine exfoliative cytology serves as the standard screening technique for bladder cancer.…”