Skip to main content

Advertisement

SpringerLink
Log in

USP28 is a potential prognostic marker for bladder cancer

  • Research Article
  • Published:
Tumor Biology

Abstract

This study was conducted to analyze the expression of the ubiquitin-specific protease Usp28 and assess its clinical significance in human bladder cancer. mRNA and protein expression levels of Usp28 were determined by real-time polymerase chain reaction (PCR) and Western blot in 24 paired bladder cancers and the adjacent non-cancerous tissues. In addition, the expression of Usp28 protein in 186 bladder cancers was also determined by immunohistochemistry. The relationship between expression of Usp28 and clinico-pathologic features and prognosis was finally evaluated. Usp28 was expressed at a higher level in bladder cancers compared to adjacent non-cancerous tissues at both the mRNA and protein levels in 24 paired samples (all P < 0.01). In immunohistochemical examination, 78 (41.9 %) of 186 cases displayed low Usp28 expression in cancerous tissues, whereas 108 (58.1 %) cases displayed high Usp28 expression. In the universal analysis, Usp28 correlated strongly with histopathological grade, clinical stage, tumor number and recurrence rate (P = 0.0001, 0.0001, 0.0001 and 0.0051, respectively), but did not correlate with gender or age (P = 0.5588 and 0.6574). After multiple analysis of the above factors and consideration of confounding factors, tumor number, histological grade, clinical stage, and recurrence were related to Usp28 expression (P = 0.001, 0.001, 0.001 and 0.001, respectively). Finally, Usp28 expression was indentified as a independent predictors of survival (P = 0.001). Usp28 protein expression is potentially valuable in prognostic evaluation of bladder cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60(5):277–300.

    Article  PubMed  Google Scholar 

  2. Edwards BK, Ward E, Kohler BA, et al. Annual report to the nation on the status of cancer, 1975–2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer. 2010;116(3):544–73.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Eissa S, Kassim S, EI-Ahmady O. Detection of bladder tumors role of cytology, morphology-based assays, biochemical and molecular markers. Curr Opin Obstet Gynecol. 2003;15(5):395–403.

    Article  PubMed  Google Scholar 

  4. Shariat SF, Karam JA, Lerner SP. Molecular markers in bladder cancer. Curr Opin Urol. 2008;18(1):1–8.

    Article  PubMed  Google Scholar 

  5. Nijman SM, Luna-Vargas MP, Velds A, et al. A genomic and functional inventory of deubiquitinating enzymes. Cell. 2005;123(5):773–86.

    Article  CAS  PubMed  Google Scholar 

  6. Popov N, Wanzel M, Madiredjo M, et al. The ubiquitin-specific protease Usp28 is required for MYC stability. Nat Cell Biol. 2007;9:765–74.

    Article  CAS  PubMed  Google Scholar 

  7. Baffa R, Letko J, McClung C, LeNoir J, Vecchione A, Gomella LG. Molecular genetics of bladder cancer: targets for diagnosis and therapy. J Exp Clin Cancer Res. 2006;25(2):145–60.

    CAS  PubMed  Google Scholar 

  8. Greene FL, Balch CM, Fleming ID, et al. AJCC cancer staging manual. 6th ed. New York: AJCC Springer-Verlag; 2002. p. 335–40.

    Book  Google Scholar 

  9. Kim WJ, Park S, Kim YJ. Biomarkers in bladder cancer: present status and perspectives. Biomark Insights. 2007;27(2):95–105.

    Google Scholar 

  10. Radeva M, Hofmann T, Altenberg B, et al. The Database dbEST correctly predicts gene expression in colon cancer patients. Curr Pharm Biotechnol. 2008;9:509–14.

    Article  Google Scholar 

  11. Garcia-España A, Salazar E, Sun TT, Wu XR, Pellicer A. Differential expression of cell cycle regulators in phenotypic variants of transgenically induced bladder tumors: implications for tumor behavior. Cancer. 2005;65(4):1150–7.

    Google Scholar 

  12. Salghetti SE, Kim SY, Tansey WP. Destruction of MYC by ubiquitin-mediated proteolysis: cancer-associated and transforming mutations stabilize MYC. EMBO J. 1999;18(3):717–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bahram F, von der Lehr N, Cetinkaya C, Larsson LG. c-MYC hot spot mutations in lymphomas result in inefficient ubiquitination and decreased proteasome-mediated turnover. Blood. 2000;95(6):2104–10.

    CAS  PubMed  Google Scholar 

  14. Welcker M, Orian A, Jin J, et al. The FBW7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation-dependent c-MYC protein degradation. Proc Natl Acad Sci U S A. 2004;101(24):9085–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Yada M, Hatakeyama S, Kamura T, et al. Phosphorylation-dependent degradation of c-MYC is mediated by the F-box protein FBW7. EMBO J. 2004;23(10):2116–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Yeh E, Cunningham M, Arnold H, et al. A signaling pathway controlling c-MYC degradation that impacts monogenic transformation of human cells. Nat Cell Biol. 2004;6(4):308–18.

    Article  CAS  PubMed  Google Scholar 

  17. Gregory MA, Hann SR. c-Myc proteolysis by the ubiquity proteasome pathway: stabilization of c-Myc in Burkitt’s lymphoma cells. Mol Cell Biol. 2000;20(7):2423–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Malempati S, Tibbitts D, Cunningham M, et al. Aberrant stabilization of c-MYC protein in some lymphoblastic leukemias. Leukemia. 2006;20(9):1572–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Flügel D, Görlach A, Kietzmann T. Glycogen synthase kinase-3β regulates cell growth, migration and angiogenesis via Fbw7 and USP-28-dependent degradation of hypoxia-inducible factor-1α. Blood. 2012;119(5):1292–301.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Peschiaroli A, Skaar JR, Pagano M, Melino G. The ubiquitin-specific protease USP47 is a novel beta-TRCP interactor regulating cell survival. Oncogene. 2010;29(9):1384–93.

    Article  CAS  PubMed  Google Scholar 

  21. Li M, Brooks CL, Kon N, Gu W. A dynamic role of HAUSP in the p53–Mdm2 pathway. Mol Cell. 2004;13(6):879–86.

    Article  CAS  PubMed  Google Scholar 

  22. Oestergaard VH, Langevin F, Kuiken HJ, et al. Deubiquitination of FANCD2 is required for DNA crosslink repair. Mol Cell. 2007;28(5):798–809.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Zhang Y, van Deursen J, Galardy PJ. Overexpression of ubiquitin specific protease 44 (USP44) induces chromosomal instability and is frequently observed in human T-cell leukemia. PLoS ONE. 2011;6(8):e23389.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant of Department of Health of Heilongjiang province (No. 2012–549).

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Department of Urinary Surgery, The First Affiliated Hospital of Harbin Medical University, 23 You Zheng Street, Harbin, 150001, Heilongjiang, China

    Guiying Guo, Yangyang Xu, Mancheng Gong, Yan Cao & Ruihua An

Authors
  1. Guiying Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yangyang Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mancheng Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yan Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ruihua An
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ruihua An.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Guo, G., Xu, Y., Gong, M. et al. USP28 is a potential prognostic marker for bladder cancer. Tumor Biol. 35, 4017–4022 (2014). https://doi.org/10.1007/s13277-013-1525-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-013-1525-1

Keywords

Search

Navigation