The authors declare that they have no competing interests.
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.
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.
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.
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.
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.
Resnick MJ, Bassett JC, Clark PE. Management of superficial and muscle-invasive urothelial cancers of the bladder. Curr Opin Oncol. 2013;25(3):281–8. PubMed
Rebouissou S, Bernard-Pierrot I, de Reynies A, Lepage ML, Krucker C, Chapeaublanc E, et al. EGFR as a potential therapeutic target for a subset of muscle-invasive bladder cancers presenting a basal-like phenotype. Sci Transl Med. 2014;6(244):244ra291. CrossRef
Cancer Genome Atlas Research N. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature. 2014;507(7492):315–22. CrossRef
Mahul-Mellier AL, Pazarentzos E, Datler C, Iwasawa R, Abuali G, Lin B, Grimm S. De-ubiquitinating protease USP2a targets RIP1 and TRAF2 to mediate cell death by TNF. Cell Death Differ. 2011; doi: 10.1038/cdd.2011.185
Epstein JI, Amin MB, Reuter VR, Mostofi FK. The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Bladder Consensus Conference Committee. Am J Surg Pathol. 1998;22(12):1435–48. CrossRefPubMed
Adam RM, Danciu T, McLellan DL, Borer JG, Lin J, Zurakowski D, et al. A nuclear form of the heparin-binding epidermal growth factor-like growth factor precursor is a feature of aggressive transitional cell carcinoma. Cancer Res. 2003;63(2):484–90. PubMed
- Assess the expression of ubiquitin specific protease USP2a for bladder cancer diagnosis
Hyung Yoon Yoon
Michael R. Freeman
- BioMed Central
Neu im Fachgebiet Urologie
Meistgelesene Bücher in der Urologie
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