Abstract
BackgroundGiven that a deubiquitinating enzyme, ubiquitin-specific protease 2a (USP2a), regulates ubiquitination, trafficking, and degradation of EGFR, which plays a critical role in bladder cancer, in this study, we aimed to quantify the USP2a gene expression, and to determine the possibility that USP2a can be used for bladder cancer diagnosis.MethodsUsing two independent cohorts (cohort 1, n = 339 in total; cohort 2, n = 140 in total) consisting of human bladder tissues from BC patients and normal controls, we analyzed the gene expression levels of USP2a. A quantitative real-time PCR amplification was performed using a Rotor Gene 6000 instrument to quantify the expression of USP2a mRNA.ResultsA comparison of 305 bladder cancers and 34 age-matched controls showed an 81.4 % reduction in USP2a expression in bladder cancers as compared to normal bladder tissues (p < 0.001). In the independent cohort consisting of 140 BC tissues and matched adjacent normal bladder tissues, the levels of USP2a in the specimens of BC patients were reduced by 86.9 % as compared to matched surrounding normal specimens from the same patients (p < 0.001). Furthermore, there was 36.3 % reduction of USP2a gene expression in muscle invasive bladder cancer (MIBC, n = 121), compared to non muscle invasive bladder cancer (NMIBC, n = 184) (p = 0.004). Lastly, USP2a mRNA expression was significantly reduced in higher stages of MIBC patients (p = 0.024), but not in NMIBC patients.ConclusionsOur findings suggest that USP2a mRNA may be considered as a diagnostic marker candidate for bladder cancer, in particular, to stratify MIBC patients with a more invasive phenotype.
Highlights
Given that a deubiquitinating enzyme, ubiquitin-specific protease 2a (USP2a), regulates ubiquitination, trafficking, and degradation of Epidermal growth factor receptor (EGFR), which plays a critical role in bladder cancer, in this study, we aimed to quantify the USP2a gene expression, and to determine the possibility that USP2a can be used for bladder cancer diagnosis
Clinical and pathological characteristics of patients with bladder cancer A previous study from our laboratory presented evidence suggesting that the USP2a deubiquitinase plays a role in bladder cancer cell proliferation using a cell culture system [11]
The characteristics of the cancer patients and controls are shown in Table 1, and further comparisons were performed in separately categorized non-muscle invasive bladder cancer (NMIBC) and Muscle invasive bladder cancer (MIBC) groups
Summary
Given that a deubiquitinating enzyme, ubiquitin-specific protease 2a (USP2a), regulates ubiquitination, trafficking, and degradation of EGFR, which plays a critical role in bladder cancer, in this study, we aimed to quantify the USP2a gene expression, and to determine the possibility that USP2a can be used for bladder cancer diagnosis. More than 90 % of bladder cancers diagnosed in the US are urothelial carcinoma, which are mostly papillary, well-, or moderately-differentiated non-muscle invasive bladder cancer (NMIBC) [5]. EGFR is known to be de-ubiqutunated by ubiquitin-specific protease 2a (USP2a) [10]. USP2a has been known to have a distinct function as a signal mediator of tumor necrosis factor-α (TNF-α)-induced cell death [17], suggesting
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