title: Assess the expression of ubiquitin specific protease USP2a for bladder cancer diagnosis.
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.
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju, Chungbuk, South Korea. leo24fly@hanmail.net.
authors.forename: Pildu
authors.initials: P
authors.lastname: Jeong
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju, Chungbuk, South Korea. yunsokha@gmail.com.
authors.forename: Yun-Sok
authors.initials: YS
authors.lastname: Ha
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju, Chungbuk, South Korea. sjyun@chungbuk.ac.kr.
authors.forename: Seok-Joong
authors.initials: SJ
authors.lastname: Yun
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju, Chungbuk, South Korea. nocks84@hanmail.net.
authors.forename: Hyung Yoon
authors.initials: HY
authors.lastname: Yoon
authors.affiliation: Departments of Surgery, Harvard Medical School, Boston, 02115, MA, USA. Michael.freeman@cshs.org.|Cancer Biology Division, Departments of Surgery and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA. Michael.freeman@cshs.org.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Freeman
authors.affiliation: Departments of Surgery, Harvard Medical School, Boston, 02115, MA, USA. Jayoung.Kim@cshs.org.|Cancer Biology Division, Departments of Surgery and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA. Jayoung.Kim@cshs.org.
authors.forename: Jayoung
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju, Chungbuk, South Korea. wjkim@chungbuk.ac.kr.
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor; D010450:Endopeptidases / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D043222:Ubiquitin Thiolesterase; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D010450:Endopeptidases; C108665:USP2 protein, human; D043222:Ubiquitin Thiolesterase