## 4 Discussion
This is in contrast to our findings, where these genes were globally up-regulated. Our finding that USP7 is globally up-regulated, is in line with two previous reports, which indicated that USP7 inhibition is a potential therapy for UBC [87; 88]. In addition, PCNA was found to be globally up-regulated in UBC. This is one of the best-studied genes in this tumor type. It is a well-known proliferation marker, related to tumor progression and anti-apoptosis; thus, it acts as an oncogene. The majority of studies agree that PCNA over-expression is related to tumor progression and survival [89; 90; 91; 92; 93]. In addition, PCNA inhibition was directly connected to UBC therapy, where it has been shown to function as an anti-tumor agent [90; 94; 95; 96]. These findings are in good agreement with our results, in which PCNA was globally up-regulated in UBC. The accumulation of various mutations may be due to exogenous or endogenous factors and is closely related to the development of carcinogenesis. There is increasing evidence that APOBEC3B is a broadly mutagenic agent in multiple tumor types [97]. It also shows increased expression, affecting the ontogenesis and progression of various cancers, including those of the neck, breast, lung, head, and bladder. The APOBECEC3B gene functions as a cytidine to uridine (C-to-U) editor, and it is heavily implicated in innate and adaptive immunity with important roles in antibody diversification and antiviral response [98]. It also plays an important role in the functions of the immune system, introducing mutations to the viral genomes [99; 100; 101; 102]. This was confirmed by our functional annotation analysis showing that the identified DEGs, manifested antiviral-related functions. It is reasonable to assume that APOBECEC3B inhibitors can prevent the accumulation of mutations in certain cancers, making it a promising therapeutic target. APOBECEC3B is often reported in the literature with the terms \"mutagen\" and \"tumor mutator\" [103; 104; 105; 106; 107]. Another interesting gene that our analysis revealed is _KRT14_. This encodes the protein keratin 14, which is a type I keratin being part of the cell skeleton of epithelial cells. The bladder epithelium, also known as the urothel, is made up of 3 different cell types. The first layer, or superficial layer, coats the inner surface of the bladder and is made up of \"umbrella cells\". The next layers consist of the intermediate and the basal layers, which come in contact with the skin. In several studies performed in mice, it has been shown that the cells of the basal layer, expressing _KRT14_, are responsible for the regeneration of urothel in the event of injury, and are cells responsible for the oncogenesis in the bladder [108; 109]. According to a previous study, _KRT14_ expression in bladder cancer is strongly associated with poor prognosis for survival, regardless of other clinical variables such as the stage of cancer, age, or sex [110]. Thus, it has been suggested that _KRT14_ is a possible prognostic biomarker for distinguishing between high and low-risk patients. Finally, we observed that the globally up-regulated genes were mostly involved in molecular functions related to the proteasome and protein-protein binding, while the annotated pathways, included viral carcinogenesis and proteasomal functions. On the other hand, the globally down-regulated genes were found to participate in different pathways in cancer, as well as basal cell carcinoma pathways.