Tumor Biology

, Volume 35, Issue 11, pp 11427–11433 | Cite as

High expression of UCH37 is significantly associated with poor prognosis in human epithelial ovarian cancer

Research Article

Abstract

Ubiquitin carboxyl-terminal hydrolase 37 (UCH37) is a member of deubiquitinating enzymes. It can suppress protein degradation through disassembling polyubiquitin from the distal subunit of the chain. The aim of this study was to assess the value of UCH37 in predicting tumor recurrence after curative resection in epithelial ovarian cancer (EOC) patients. In this study, the expression level of UCH37 in 5 paired EOC and normal tissue was tested by Western blot. And the association of UCH37 expression and prognostic value was analyzed in 100 tumor specimens from EOC patients, who underwent curative resection between 2003 and 2011. We found that UCH37 was up-regulated in most of the tumor tissue and high expression of UCH37 was an independent significant predictor associated with the poor outcome and recurrence of EOC (p = 0.0037 and p = 0.0042 in overall and disease-free survival, respectively), especially in the advanced stage of EOC (p = 0.0106 and p = 0.0115 in overall and disease-free survival, respectively), and may become a novel predictor for prognosis of EOC patients after curative resection. Our data suggest for the first time that UCH37 overexpression is associated with advanced tumor progression and poor clinical outcome of EOC patients and may help physicians make informed decisions regarding adjuvant treatment following curative resection.

Keywords

UCH37 EOC Prognosis Predictor 

Notes

Acknowledgments

The authors would like to express gratitude to the staff of Prof. Xi-zhong Shen’s laboratory for their critical discussion and reading of the manuscript. The study was partly funded by the Youth Foundation of Zhongshan Hospital (ZSQN2012-36).

Conflicts of interest

None

References

  1. 1.
    Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. Cancer J Clin. 2014;64(1):9–29. doi: 10.3322/caac.21208.CrossRefGoogle Scholar
  2. 2.
    Wright JD, Shah M, Mathew L, Burke WM, Culhane J, Goldman N, et al. Fertility preservation in young women with epithelial ovarian cancer. Cancer. 2009;115(18):4118–26. doi: 10.1002/cncr.24461.PubMedCrossRefGoogle Scholar
  3. 3.
    Rota M, Pasquali E, Scotti L, Pelucchi C, Tramacere I, Islami F, et al. Alcohol drinking and epithelial ovarian cancer risk a systematic review and meta-analysis. Gynecol Oncol. 2012;125(3):758–63. doi: 10.1016/j.ygyno.2012.03.031.PubMedCrossRefGoogle Scholar
  4. 4.
    Hershko A, Ciechanover A. The ubiquitin system. Annu Rev Biochem. 1998;67:425–79. doi: 10.1146/annurev.biochem.67.1.425.PubMedCrossRefGoogle Scholar
  5. 5.
    Pickart CM. Mechanisms underlying ubiquitination. Annu Rev Biochem. 2001;70:503–33. doi: 10.1146/annurev.biochem.70.1.503.PubMedCrossRefGoogle Scholar
  6. 6.
    Glickman MH, Ciechanover A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev. 2002;82(2):373–428. doi: 10.1152/physrev.00027.2001.PubMedGoogle Scholar
  7. 7.
    Wilkinson KD. Cell biology: unchaining the condemned. Nature. 2002;419(6905):351–3. doi: 10.1038/419351a.PubMedCrossRefGoogle Scholar
  8. 8.
    Goldberg AL. Protein degradation and protection against misfolded or damaged proteins. Nature. 2003;426(6968):895–9. doi: 10.1038/nature02263.PubMedCrossRefGoogle Scholar
  9. 9.
    Chung CH, Baek SH. Deubiquitinating enzymes: their diversity and emerging roles. Biochem Biophys Res Commun. 1999;266(3):633–40. doi: 10.1006/bbrc.1999.1880.PubMedCrossRefGoogle Scholar
  10. 10.
    Chen YJ, Ma YS, Fang Y, Wang Y, Fu D, Shen XZ. Power and promise of ubiquitin carboxyl-terminal hydrolase 37 as a target of cancer therapy. Asian Pacific journal of cancer prevention : APJCP. 2013;14(4):2173–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Al-Shami A, Jhaver KG, Vogel P, Wilkins C, Humphries J, Davis JJ, et al. Regulators of the proteasome pathway, Uch37 and Rpn13, play distinct roles in mouse development. PLoS One. 2010;5(10):e13654. doi: 10.1371/journal.pone.0013654.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Rolen U, Kobzeva V, Gasparjan N, Ovaa H, Winberg G, Kisseljov F, et al. Activity profiling of deubiquitinating enzymes in cervical carcinoma biopsies and cell lines. Mol Carcinog. 2006;45(4):260–9. doi: 10.1002/mc.20177.PubMedCrossRefGoogle Scholar
  13. 13.
    Chen Y, Fu D, Xi J, Ji Z, Liu T, Ma Y, et al. Expression and clinical significance of UCH37 in human esophageal squamous cell carcinoma. Dig Dis Sci. 2012;57(9):2310–7. doi: 10.1007/s10620-012-2181-9.PubMedCrossRefGoogle Scholar
  14. 14.
    Fang Y, Mu J, Ma Y, Ma D, Fu D, Shen X. The interaction between ubiquitin C-terminal hydrolase 37 and glucose-regulated protein 78 in hepatocellular carcinoma. Mol Cell Biochem. 2012;359(1–2):59–66. doi: 10.1007/s11010-011-0999-7.PubMedCrossRefGoogle Scholar
  15. 15.
    Fang Y, Fu D, Tang W, Cai Y, Ma D, Wang H, et al. Ubiquitin C-terminal Hydrolase 37, a novel predictor for hepatocellular carcinoma recurrence, promotes cell migration and invasion via interacting and deubiquitinating PRP19. Biochim Biophys Acta. 2013;1833(3):559–72. doi: 10.1016/j.bbamcr.2012.11.020.PubMedCrossRefGoogle Scholar
  16. 16.
    Fang Y, Fu D, Shen XZ. The potential role of ubiquitin c-terminal hydrolases in oncogenesis. Biochim Biophys Acta. 2010;1806(1):1–6. doi: 10.1016/j.bbcan.2010.03.001.PubMedGoogle Scholar
  17. 17.
    Wang L, Chen YJ, Hou J, Wang YY, Tang WQ, Shen XZ et al. Expression and clinical significance of BIRC6 in human epithelial ovarian cancer. Tumour biology: the journal of the International Society for Oncodevelopmental Biology and Medicine. 2014. doi: 10.1007/s13277-014-1641-6.

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.Department of Obstetrics and Gynecology, Shanghai Zhongshan HospitalFudan UniversityShanghaiChina
  2. 2.Department of Gastroenterology, Zhongshan HospitalFudan UniversityShanghaiChina

Personalised recommendations