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Published in: Tumor Biology 5/2014

01-05-2014 | Research Article

USP28 is a potential prognostic marker for bladder cancer

Authors: Guiying Guo, Yangyang Xu, Mancheng Gong, Yan Cao, Ruihua An

Published in: Tumor Biology | Issue 5/2014

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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.
Literature
1.
2.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
3.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
4.
go back to reference Shariat SF, Karam JA, Lerner SP. Molecular markers in bladder cancer. Curr Opin Urol. 2008;18(1):1–8.CrossRefPubMed Shariat SF, Karam JA, Lerner SP. Molecular markers in bladder cancer. Curr Opin Urol. 2008;18(1):1–8.CrossRefPubMed
5.
go back to reference Nijman SM, Luna-Vargas MP, Velds A, et al. A genomic and functional inventory of deubiquitinating enzymes. Cell. 2005;123(5):773–86.CrossRefPubMed Nijman SM, Luna-Vargas MP, Velds A, et al. A genomic and functional inventory of deubiquitinating enzymes. Cell. 2005;123(5):773–86.CrossRefPubMed
6.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
7.
go back to reference 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.PubMed 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.PubMed
8.
go back to reference Greene FL, Balch CM, Fleming ID, et al. AJCC cancer staging manual. 6th ed. New York: AJCC Springer-Verlag; 2002. p. 335–40.CrossRef Greene FL, Balch CM, Fleming ID, et al. AJCC cancer staging manual. 6th ed. New York: AJCC Springer-Verlag; 2002. p. 335–40.CrossRef
9.
go back to reference Kim WJ, Park S, Kim YJ. Biomarkers in bladder cancer: present status and perspectives. Biomark Insights. 2007;27(2):95–105. Kim WJ, Park S, Kim YJ. Biomarkers in bladder cancer: present status and perspectives. Biomark Insights. 2007;27(2):95–105.
10.
go back to reference 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.CrossRef 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.CrossRef
11.
go back to reference 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. 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.
12.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
13.
go back to reference 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.PubMed 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.PubMed
14.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
15.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
16.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
17.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
18.
19.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
20.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
21.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
22.
23.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
Metadata
Title
USP28 is a potential prognostic marker for bladder cancer
Authors
Guiying Guo
Yangyang Xu
Mancheng Gong
Yan Cao
Ruihua An
Publication date
01-05-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 5/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1525-1

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