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Background  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.    Methods  Using 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.    Results  A 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.    Conclusions  Our 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.

Assess the expression of ubiquitin specific protease USP2a for bladder cancer diagnosis