Potential of Proteases in the Diagnosis of Bladder Cancer

Bladder carcinoma (BC) is evaluated as the ninth most common cancer worldwide and the sixth most common cancer among men. The determination of the occurrence and stage of the disease is a significant diagnostic task. An alternative to an invasive biopsy may be the determination of biomarkers in patient samples such as bladder tissue, blood serum, plasma, or urine samples. The aim of this paper is to review reports on the role of proteases in bladder cancer and their determination in cancerous samples. Proteases can be classified in several groups depending on their catalytic residue, most commonly aspartic, cysteine, serine, metalloproteinases, and others. A review was made of papers reporting cysteine cathepsins: B, L, H, V, S, aspartyl cathepsin D, and metalloproteinases MMP 1, 2, 3, 7, 9, 10, 14, and 15, as well as ubiquitin-specific proteases USP 1, 2a and 5. The majority of the reviewed papers show an increase in marker concentration in bladder cancer samples versus a control. Only a few of them provide quantitative information about MMP biomarkers in bladder tissue (cancerous and control tissue), and none give such information about cathepsins. Levels of the order of µg/g protein are characteristic of MMP biomarkers in urinary bladder tissue. Most reported concentrations of proteases in blood serum/plasma and urine are at levels of ng/mL, both cancerous and control samples. It is concluded that the reviewed papers do not provide a clear picture concerning the use of proteases as bladder cancer biomarkers or concerning the levels of particular proteases in control samples. Potential new analytical tools for protease determination are discussed. More work in this area is necessary, especially by scientists equipped with new analytical tools.