Urine as an emerging liquid biopsy for bladder cancer biomarker detection
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Bladder cancer reoccurrence rates are high
Bladder cancer is the sixth most prevalent cancer worldwide in both men and women, with incidence and mortality increasing year by year (1).
In general, the most common type of bladder cancer begins as a non-muscle invasive urothelial carcinoma of the urinary bladder, which is localized to the region inside of the organ (1,2). The 5-year survival rate for localized bladder cancer is 70% (2), highlighting the importance of early screening and detection.
However, recurrence rates are high, with progression to muscle invasive urothelial carcinoma of the urinary bladder seen in 15% of patients. As a result, regular follow-ups are necessary. Guidelines suggest a combination of cystoscopy, cytology, and imaging for surveillance of patients with UCB (urinary cancer of the bladder). These procedures are intensive, making bladder cancers one of the most expensive cancers to monitor (1).
Current detection methods for bladder cancer are invasive and/or offer poor sensitivity
Currently, two methods are commonly used to detect bladder cancer (1):
- Cystoscopy involves inserting a cystoscope to observe changes in the bladder. In general cystoscopy has high sensitivity, however, small tumors can be missed. This procedure is also invasive, highly uncomfortable and clinician dependent.
- Urine cytology involves observing a urine sample under a microscope for any abnormal changes. Together with cystoscopy, this test can be used in the diagnosis and follow-up of bladder cancer. While cytology is non-invasive, and inexpensive it has an overall low sensitivity.
As both cystoscopy and cytology may not always be feasible or accurate to follow repeatedly, finding alternative methods can improve the quality of life of patients with bladder cancer.
Urine as a promising sample type for bladder cancer screening and detection
Given the function of the bladder, and its proximity to the urinary tract, urine as a sample type is particularly attractive as it can contain potential biomarkers for bladder cancer detection. Urine is also an exciting sample type as it allows for non-invasive, inexpensive sample collection, as well as offers the possibility of repeated sampling. These benefits can help overcome many of the challenges with the current detection methods. There are a range of commercially available urinary biomarker tests and kits for bladder cancer detection (1).
(I) Genomic biomarkers
One particularly interesting biomarker that has shown to be a game-changer for disease monitoring and early detection of recurrence in bladder cancer is telomerase reverse transcriptase (TERT) promotor mutations. These mutations are extremely specific to bladder cancer (1). Additionally, mutations in RASMAPK (mitogen-activated protein kinase) pathway can also provide bladder cancer biomarker candidates(1).
(II) Epigenomic biomarkers
Epigenetic factors can also play an important role in bladder cancer development, and can be a strong indicator for disease development. Several studies have shown the role of DNA methylation and methylated genes in influencing gene expression (1).
(III) Transcriptomic biomarkers
Studies indicate specific miRNA levels could indicate bladder cancer as well as disease stage. Evidence also suggest miRNA levels in urine can suggest bladder cancer relapse, however, more work is needed in this space (2).
(IV) Proteomic biomarkers
Several urinary protein biomarkers for bladder cancer have been identified, including urinary calprotectin. One study showed the median calprotectin level was 10-fold higher in patients with bladder cancer than healthy controls. Urinary proteins, stathmin-1 and CD147 have also shown potential in bladder cancer detection (1).
(V) Metabolomic biomarkers
A number of urinary metabolites for bladder cancer have been identified. A study profiling urine metabolites found several metabolites that distinguished the disease from control groups with a high sensitivity and specificity (1).
Future perspectives
Given the wide array of biomarkers, urine is a promising sample type that can change the way the disease is detected and monitored in the future. However, for effective clinical applications, standardization of preanalytical conditions for the handling of urine specimens is required. More work needs to be done to better understand if factors such as method of urine collection, urine fractions, and the need for urine preservation can influence biomarker detection for bladder cancer. Novosanis' Colli-Pee®, a urine collection device, which can be prefilled with a preservative, allows for volumetric collection of different urine volumes, and has shown potential for urinary biomarker detection for several cancer types.
White Paper: Urine as a liquid biopsy
White Paper: Urine as a sample type for multi-omic cancer research
References:
- White paper: Urine as an emerging liquid biopsy for bladder cancer biomarkers https://novosanis.com/sites/default/files/poster/pdf/Urine%20as%20an%20e...
- Bladder cancer webpage: https://novosanis.com/bladder-cancer
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