Oncology

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Liquid biopsy – Urine as a sample type

Early detection of cancer can greatly increase chances of survival and improve overall quality of life. Traditionally, a tissue biopsy is the common approach to diagnose many cancers. However, obtaining a tissue sample is not always feasible and the process can be invasive, painful, expensive, time intensive, difficult to perform and requires the intervention of a clinician (1). Further, due to intratumor heterogeneity, a tissue biopsy may not always reflect the entire tumor landscape.

As a result, researchers are continuously exploring alternative methods to detect cancer types. The use of minimally invasive procedures such as liquid biopsies in biological fluids such as blood and urine are evolving rapidly (1)

Circulating molecules such as cell-free DNA, circulating tumor cells, circulating RNAs, proteins, peptides and exosomes present in biological fluids has the potential to provide a full landscape of primary and metastatic tumor markers.

Liquid biopsies have several advantages - they allow (repeated) sampling, and can better reflect the genetic profile of all tumor subclones. Additionally, they are associated with less complications, and are less invasive than traditional biopsies (1).

The most often used liquid biopsy is blood, which uses either serum or plasma as a sample type. However, blood as a liquid biopsy also has several limitations. Blood contains a relatively high and complex protein repertoire, that can interfere with biomarker measurements. Additionally, blood sampling is relatively invasive, and can pose a risk of infection for both the patient and the caregiver (2).

Alternatively, urine as a liquid biopsy offers several benefits. Urine is easily accessible, non-invasive, available in larger quantities and can easily be collected at home by an individual (3). Moreover, urine sampling does not hold any risk of transmission of blood-borne pathogens (4).

In addition, urine testing enables cost-efficient serial sampling. In terms of analysis, as urine is filtered by the kidney before release, its low protein content in theory makes isolation of DNA easier than blood (2,3).

Several studies have shown that the use of urine as a liquid biopsy for cancer detection and monitoring is promising. It has the potential to improve screening and detection of several cancer types including prostate, cervical, bladder, and kidney cancer, but surprisingly also in breast, colon and lung cancer (5,6,7,8).

References:

  1. Di Meo A, Bartlett J, Cheng Y, Pasic MD, Yousef GM. Liquid biopsy: a step forward towards precision medicine in urologic malignancies. Mol Cancer. 2017;16(1):80.

  2. Su YH, Wang M, Brenner DE, et al. Human urine contains small, 150 to 250 nucleotidesized, soluble DNA derived from the circulation and may be useful in the detection of colorectal cancer. J Mol Diagn. 2004;6(2):101-107.

  3. Nolen BM, Lokshin AE. -The advancement of biomarker-based diagnostic tools for ovarian, breast, and pancreatic cancer through the use of urine as an analytical biofluid. Int J Biol Markers. 2011;26(3):141-152.

  4. CDC. The National Healthcare Safety Network (NHSN) Manual. 2013. USA

  5. Liu Z, Liu W. Association of urinary and plasma DNA in early breast cancer patients and its links to disease relapse. Clin Transl Oncol. 2018;20(8):1053-1060

  6. Fujita K, Nonomura N. Urinary biomarkers of prostate cancer. Int J Urol. 2018;25(9):770-779.

  7. Krishnamurthy N, Spencer E, Torkamani A, Nicholson L. Liquid Biopsies for Cancer: Coming to a Patient near You. J Clin Med. 2017;6(1).

  8. Theodorescu D, Schiffer E, Bauer HW, et al. Discovery and validation of urinary biomarkers for prostate cancer. Proteomics Clin Appl. 2008;2(4):556-570.

 

 

Prostate cancer

To successfully cure patients with prostate cancer it is important to detect the disease at an early stage. Current screening techniques are based on a measurement of serum prostate specific antigen (PSA) levels and a digital rectal examination (DRE). Drawbacks of PSA testing are its low sensitivity and specificity. Because of the ease of collection and the fact that prostate cells are directly released into the urethra through prostatic ducts after DRE or prostate massage, urine has become the future of non-invasive biomarker testing.

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Cervical cancer

Strains of HPV, in particular HPV16 and 18 have been linked to cause most cervical cancer cases. This cancer type usually does not present any symptoms until it reaches an advanced stage, making early detection and treatment challenging. While women are invited to have a cervical sample through public screening programs, participation remains low in many areas. Urine can help increase participation and reach women that traditionally do not participate in cervical cancer screening programs.

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