Skip to main content

Advertisement

Log in

Expression and Clinical Significance of UCH37 in Human Esophageal Squamous Cell Carcinoma

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Ubiquitin carboxyl-terminal hydrolase 37 (UCH37), a member of the DUBs, was found to play an important role in oncogenesis through promoting some Proto-oncogenes’ expression and stem cell-like characteristics in the cell in previous research. The aim of this study was to assess the value of UCH37 in predicting tumor recurrence after curative resection in esophageal squamous cell carcinoma (ESCC) patients.

Methods

We analyzed UCH37 protein expression in 111 clinicopathologically characterized ESCC cases, from those who underwent curative resection between 2007 and 2008, by immunohistochemistry. The prognostic significance was assessed using Kaplan–Meier survival estimates and log-rank tests.

Results

We found that UCH37 expression was higher in the cancer tissue than in non-tumorous control tissue at protein level and was overexpressed in tumor tissues of recurrent patients. There was a significant difference of UCH37 expression in patients categorized according to TNM stage (p = 0.038) and lymph nodes metastasis condition (p = 0.009). Univariate analyses revealed that UCH37 was a significant predictor for overall survival and disease-free survival, and multivariate analyses showed that UCH37 was an independent prognostic marker for ESCC recurrence. A prognostic significance of UCH37 was also found in the subgroup of lymph nodes metastasis condition classification. About 90 % of the recurrent patients recurred within 2 years, of which 84.4 % were predicted by UCH37.

Conclusion

UCH37 is associated with outcome and recurrence of ESCC and can be a novel predictor for poor prognosis of ESCC patients after curative resection.

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

Access this article

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

Similar content being viewed by others

References

  1. Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 2006;24:2137–2150.

    Article  PubMed  Google Scholar 

  2. Day NE, Varghese C. Oesophageal cancer. Cancer Surv. 1994;19–20:43–54.

    PubMed  Google Scholar 

  3. Younes M, Henson DE, Ertan A, Miller CC. Incidence and survival trends of esophageal carcinoma in the United States: racial and gender differences by histological type. Scand J Gastroenterol. 2002;37:1359–1365.

    Article  PubMed  CAS  Google Scholar 

  4. Vallbohmer D, Lenz HJ. Predictive and prognostic molecular markers in outcome of esophageal cancer. Dis Esophagus. 2006;19:425–432.

    Article  PubMed  CAS  Google Scholar 

  5. Hershko A, Ciechanover A. The ubiquitin system. Annu Rev Biochem. 1998;67:425–479.

    Article  PubMed  CAS  Google Scholar 

  6. Pickart CM. Mechanisms underlying ubiquitination. Annu Rev Biochem. 2001;70:503–533.

    Article  PubMed  CAS  Google Scholar 

  7. Finley D, Ciechanover A, Varshavsky A. Ubiquitin as a central cellular regulator. Cell. 2004;116:S29–S32.

    Article  PubMed  CAS  Google Scholar 

  8. Sridhar VV, Kapoor A, Zhang K, Zhu J, et al. Control of DNA methylation and heterochromatic silencing by histone H2B deubiquitination. Nature. 2007;447:735–738.

    Article  PubMed  CAS  Google Scholar 

  9. Liu H, Buus R, Clague MJ, Urbe S. Regulation of ErbB2 receptor status by the proteasomal DUB POH1. PLoS ONE. 2009;4:e5544.

    Article  PubMed  Google Scholar 

  10. Singhal S, Taylor MC, Baker RT. Deubiquitylating enzymes and disease. BMC Biochem. 2008;9:S3.

    Article  PubMed  Google Scholar 

  11. Yao T, Song L, Xu W, DeMartino GN, et al. Proteasome recruitment and activation of the Uch37 deubiquitinating enzyme by Adrm1. Nat Cell Biol. 2006;8:994–1002.

    Article  PubMed  CAS  Google Scholar 

  12. Schreiner P, Chen X, Husnjak K, Randles L, et al. Ubiquitin docking at the proteasome through a novel pleckstrin-homology domain interaction. Nature. 2008;453:548–552.

    Article  PubMed  CAS  Google Scholar 

  13. Husnjak K, Elsasser S, Zhang N, Chen X, et al. Proteasome subunit Rpn13 is a novel ubiquitin receptor. Nature. 2008;453:481–488.

    Article  PubMed  CAS  Google Scholar 

  14. Hamazaki J, Iemura S, Natsume T, Yashiroda H, et al. A novel proteasome interacting protein recruits the deubiquitinating enzyme UCH37 to 26S proteasomes. EMBO J. 2006;25:4524–4536.

    Article  PubMed  CAS  Google Scholar 

  15. Qiu XB, Ouyang SY, Li CJ, Miao S, et al. hRpn13/ADRM1/GP110 is a novel proteasome subunit that binds the deubiquitinating enzyme, UCH37. EMBO J. 2006;25:5742–5753.

    Article  PubMed  CAS  Google Scholar 

  16. Wicks SJ, Haros K, Maillard M, Song L, et al. The deubiquitinating enzyme UCH37 interacts with Smads and regulates TGF-beta signalling. Oncogene. 2005;24:8080–8084.

    Article  PubMed  CAS  Google Scholar 

  17. Wicks SJ, Grocott T, Haros K, Maillard M, et al. Reversible ubiquitination regulates the Smad/TGF-beta signalling pathway. Biochem Soc Trans. 2006;34:761–763.

    Article  PubMed  CAS  Google Scholar 

  18. Cutts AJ, Soond SM, Powell S, Chantry A. Early phase TGFbeta receptor signalling dynamics stabilised by the deubiquitinase UCH37 promotes cell migratory responses. Int J Biochem Cell Biol. 2011;43:604–612.

    Article  PubMed  CAS  Google Scholar 

  19. Chen Z, Niu X, Li Z, Yu Y, et al. Effect of ubiquitin carboxy-terminal hydrolase 37 on apoptotic in A549 cells. Cell Biochem Funct. 2011;29:142–148.

    Article  PubMed  Google Scholar 

  20. Rolen U, Kobzeva V, Gasparjan N, Ovaa H, et al. Activity profiling of deubiquitinating enzymes in cervical carcinoma biopsies and cell lines. Mol Carcinog. 2006;45:260–269.

    Article  PubMed  CAS  Google Scholar 

  21. Fang Y, Mu J, Ma Y, Ma D, et al. The interaction between ubiquitin C-terminal hydrolase 37 and glucose-regulated protein 78 in hepatocellular carcinoma. Mol Cell Biochem. 2012;359:59–66.

    Article  PubMed  CAS  Google Scholar 

  22. Kapuria V, Peterson LF, Fang D, Bornmann WG, et al. Deubiquitinase inhibition by small-molecule WP1130 triggers aggresome formation and tumor cell apoptosis. Cancer Res. 2010;70:9265–9276.

    Article  PubMed  CAS  Google Scholar 

  23. Al-Shami A, Jhaver KG, Vogel P, Wilkins C, et al. Regulators of the proteasome pathway, Uch37 and Rpn13, play distinct roles in mouse development. PLoS ONE. 2010;5:e13654.

    Article  PubMed  Google Scholar 

  24. Fang Y, Fu D, Shen XZ. The potential role of ubiquitin c-terminal hydrolases in oncogenesis. Biochim Biophys Acta. 2010;1806:1–6.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to express gratitude to the staff of Prof. Xizhong Shen’s laboratory for their critical discussion and reading of the manuscript and the members of the Department of Thoracic Surgery of Zhongshan Hospital for their tumor specimens and follow-up data. This study was supported by the Shanghai Science and Technology Commission (10410709400, 10411950100), National Nature Science Foundation of China (81000968, 81101540, 81101637 and 81172273) and the National Clinical Key Special Subject of China.

Conflict of interest

The authors declare that there are no conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Qun Wang or Xizhong Shen.

Additional information

Yanjie Chen and Da Fu contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, Y., Fu, D., Xi, J. et al. Expression and Clinical Significance of UCH37 in Human Esophageal Squamous Cell Carcinoma. Dig Dis Sci 57, 2310–2317 (2012). https://doi.org/10.1007/s10620-012-2181-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-012-2181-9

Keywords

Navigation