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01.12.2015 | Research article | Ausgabe 1/2015 Open Access

BMC Urology 1/2015

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

Zeitschrift:
BMC Urology > Ausgabe 1/2015
Autoren:
Pildu Jeong, Yun-Sok Ha, Seok-Joong Yun, Hyung Yoon Yoon, Michael R. Freeman, Jayoung Kim, Wun-Jae Kim
Wichtige Hinweise

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

PJ and YH performed experiments, and participated data interpretation. SY and HY participated in the design of the study and performed the statistical analysis. JK and WK supervised study design and experiments, and led obtaining funding. SY and JK drafted the manuscript. MF participated critical revision of the manuscript. All authors read and approved the final manuscript.

Abstract

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.
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