Tumor Biology

, Volume 37, Issue 7, pp 8917–8922 | Cite as

High expression of constitutive photomorphogenic 1 (COP1) is associated with poor prognosis in bladder cancer

  • Jianlong Li
  • Longwang Wang
  • Ruihai Xiao
  • Qiufeng Pan
  • Hongwei Huang
  • Renrui Kuang
Original Article


The present study was to investigate the expression and prognostic value of constitutive photomorphogenic 1 (COP1) in bladder cancer. In our study, real-time quantitative PCR (RT-PCR) was performed to detect 10 pairs of fresh bladder cancer (BCa) and adjacent noncancerous tissues. In addition, immunohistochemistry was utilized to detect the expression of COP1 in 174 clinical bladder cancer samples. What is more, the correlation of COP1 expression and clinicopathological features and clinical outcomes were analyzed. The expression levels of COP1 in clinical bladder cancer were much higher than that in paired adjacent noncancerous tissues (p < 0.0001). High expression of COP1 was closely related with differentiation (p = 0.040) and recurrence (p = 0.001) of patients with bladder cancer. Kaplan-Meier analysis revealed that the expression of COP1 was closely correlated with overall survival (p = 0.048) of bladder cancer, while, recurrence-free survival (p = 0.201). Moreover, Cox multivariate regression analyses showed that COP1 expression was an independent predictor of overall survival (OS; p = 0.027, hazard ratio = 2.127, confidence interval 0.814 to 9.736). Based on our data, the present study suggests that high expression of COP1 may be a novel biological indicator for evaluation of poor prognosis in bladder cancer.


COP1 expression Bladder cancer Prognosis 


Compliance with ethical standards

Conflicts of interest

The authors declare that they have no competing interests.


  1. 1.
    Stenzl A, Cowan NC, De Santis M, et al. Treatment of muscle-invasive and metastatic bladder cancer: update of the EAU guidelines. Eur Urol. 2011;59(6):1009–18.CrossRefPubMedGoogle Scholar
  2. 2.
    Zhu Z, Wang X, Shen Z, Lu Y, Zhong S, Xu C. Risk of bladder cancer in patients with diabetes mellitus: an updated meta-analysis of 36 observational studies. BMC Cancer. 2013;13:310.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer Journal international du cancer. 2015;136(5):E359–386.CrossRefPubMedGoogle Scholar
  4. 4.
    van Rhijn BW, Burger M, Lotan Y, et al. Recurrence and progression of disease in non-muscle-invasive bladder cancer: from epidemiology to treatment strategy. Eur Urol. 2009;56(3):430–42.CrossRefPubMedGoogle Scholar
  5. 5.
    Ather MH, Nazim SM. New and contemporary markers of prognosis in nonmuscle invasive urothelial cancer. Korean J Urology. 2015;56(8):553–64.CrossRefGoogle Scholar
  6. 6.
    Oderda M, Ricceri F, Pisano F, et al. Prognostic factors including Ki-67 and p53 in Bacillus Calmette-Guerin-treated non-muscle-invasive bladder cancer: a prospective study. Urol Int. 2013;90(2):184–90.CrossRefPubMedGoogle Scholar
  7. 7.
    Lokeshwar VB, Schroeder GL, Selzer MG, et al. Bladder tumor markers for monitoring recurrence and screening comparison of hyaluronic acid-hyaluronidase and BTA-Stat tests. Cancer. 2002;95(1):61–72.CrossRefPubMedGoogle Scholar
  8. 8.
    Jones A, Crew J. Vascular endothelial growth factor and its correlation with superficial bladder cancer recurrence rates and stage progression. Urol Clin North Am. 2000;27(1):191–7.CrossRefPubMedGoogle Scholar
  9. 9.
    Soloway MS, Briggman V, Carpinito GA, et al. Use of a new tumor marker, urinary NMP22, in the detection of occult or rapidly recurring transitional cell carcinoma of the urinary tract following surgical treatment. J Urol. 1996;156(2 Pt 1):363–7.CrossRefPubMedGoogle Scholar
  10. 10.
    Deng XW, Caspar T, Quail PH. cop1: a regulatory locus involved in light-controlled development and gene expression in Arabidopsis. Genes Dev. 1991;5(7):1172–82.CrossRefPubMedGoogle Scholar
  11. 11.
    Dornan D, Wertz I, Shimizu H, et al. The ubiquitin ligase COP1 is a critical negative regulator of p53. Nature. 2004;429(6987):86–92.CrossRefPubMedGoogle Scholar
  12. 12.
    Li YF, Wang DD, Zhao BW, et al. High level of COP1 expression is associated with poor prognosis in primary gastric cancer. Int J Biol Sci. 2012;8(8):1168–77.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Dornan D, Bheddah S, Newton K, et al. COP1, the negative regulator of p53, is overexpressed in breast and ovarian adenocarcinomas. Cancer Res. 2004;64(20):7226–30.CrossRefPubMedGoogle Scholar
  14. 14.
    Azemar MD, Comperat E, Richard F, Cussenot O, Roupret M. Bladder recurrence after surgery for upper urinary tract urothelial cell carcinoma: frequency, risk factors, and surveillance. Urol Oncol. 2011;29(2):130–6.CrossRefPubMedGoogle Scholar
  15. 15.
    Corcoran CA, Huang Y, Sheikh MS. The p53 paddy wagon: COP1, Pirh2 and MDM2 are found resisting apoptosis and growth arrest. Cancer Biol Ther. 2004;3(8):721–5.CrossRefPubMedGoogle Scholar
  16. 16.
    Mariani O, Brennetot C, Coindre JM, et al. JUN oncogene amplification and overexpression block adipocytic differentiation in highly aggressive sarcomas. Cancer Cell. 2007;11(4):361–74.CrossRefPubMedGoogle Scholar
  17. 17.
    Wei W, Kaelin Jr WG. Good COP1 or bad COP1? In vivo veritas. J Clin Invest. 2011;121(4):1263–5.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Marine JC. Spotlight on the role of COP1 in tumorigenesis. Nat Rev Cancer. 2012;12(7):455–64.CrossRefPubMedGoogle Scholar
  19. 19.
    Vitari AC, Leong KG, Newton K, et al. COP1 is a tumour suppressor that causes degradation of ETS transcription factors. Nature. 2011;474(7351):403–6.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Jianlong Li
    • 1
  • Longwang Wang
    • 1
  • Ruihai Xiao
    • 1
  • Qiufeng Pan
    • 1
  • Hongwei Huang
    • 1
  • Renrui Kuang
    • 1
  1. 1.Department of Urologythe Second Affiliated Hospital of Nanchang UniversityNanchangPeople’s Republic of China

Personalised recommendations