## 1 Introduction  
Urinary bladder cancer (BCa) is the 10 th most common cancer in the world, with an estimated 549,393 diagnosed cases and 200,000 deaths annually. It is the 6 th most common malignancy in males and the 17 th in females, with age-standardised risks of 9.6% and 2.4%, respectively [1]. This disease can present as non-muscle-invasive bladder cancer (NMIBC), muscle-invasive bladder cancer (MIBC), or the metastatic form of the disease. Tobacco smoking is the most important risk factor for BCa: it is responsible for approximately half of BCa cases and is associated with poor oncological outcomes for both NMIBC and MIBC [2]. Stopping smoking reduces the risk of developing BC by almost 40% within 5 years [3]. Bladder cancer remains a highly prevalent and lethal malignancy. The optimal selection of treatment depends on early diagnosis and accurate staging and grading. Biomarkers are critical in routine clinical practice. They serve as indicators for the detection of bladder carcinoma and for the prediction of its recurrence and progression. A number of bladder cancer markers are described in the literature [4]. Numerous reports have demonstrated that an aberrant process of the ubiquitin-proteasome system results in the disturbance of protein degradation. This disturbance can lead to tumourigenesis [5; 6]. Increased concentrations of circulating proteasomes have been demonstrated in patients with multiple myeloma [7], acute leukaemia [8], malignant melanoma [9], and various solid tumours [10; 11]. Studies have demonstrated that ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) is implicated in oncogenesis, tumour cell invasion, and metastasis [12; 13; 14]. The expression of UCH-L1 has been reported in a variety of cancers [15]. The literature data suggest that UCH-L1 may play a role as a prognostic marker for tumour growth and progression [16; 17; 18; 19]. The relationship between the ubiquitin-proteasome system and cancer progression has become a topic of increasing interest. The ubiquitin-proteasome system (UPS) is involved in intracellular protein degradation and the regulation of many cellular processes such as the cell cycle, induction of immune response, and gene expression [20; 21; 22]. These processes are highly relevant to tumour progression and carcinogenesis [23]. The UPS has several components, including ubiquitin, 26S proteasome, ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), ubiquitin-ligating enzyme (E3), and deubiquitinating enzymes (DUBs) [6; 20]. The central element of this system is the 26S proteasome. This is a multi-subunit proteolytic complex, consisting of the 19S regulatory particle and the 20S core particle. The 19S subunit is responsible for substrate recognition, deubiquitin, and unfolding, while the 20S proteasome is responsible for proteolytic activity and protein degradation. The 20S proteasome (M \(\sim\)700 kDa) has a cylindrical structure and is composed of two outer rings and two inner rings. The outer rings contain \(\alpha\)-type subunits, whose function is to control the entry of the substrate proteins into the central catalytic chamber and bind the regulators. The inner rings contain \(\beta\)-type subunits. Three of the \(\beta\)-subunits, \(\lx@sectionsign\)1, \(\lx@sectionsign\)2, and \(\lx@sectionsign\)5, are catalytically active and are responsible, respectively, for the caspase-like (or peptidylglutamyl-peptide), trypsin-like, and chymotrypsin-like hydrolysing functions [24]. The processes of ubiquitination and deubiquitination play a very important role in protein degradation in the proteasome. Prior to the entry of protein into the proteasome, the deubiquitinating enzymes (DUBs) remove ubiquitin from the substrate proteins. Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), also known as PGP9.5, is one of the deubiquitining enzymes. UCH-L1 belongs to the family of peptidases. This enzyme hydrolyses a peptide bond at the C-terminal glycine of ubiquitin [25] and is a mono-ubiquitin stabiliser [26].