Skip to main content

Advertisement

Log in

Reduced expression of Dicer11 is associated with poor prognosis in patients with nasopharyngeal carcinoma

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Dicer11 plays an important role in generation of microRNA and is dysregulated in a variety of human cancers. The purpose of this study was to evaluate Dicer11 expression and its prognostic value in nasopharyngeal carcinoma (NPC). The protein expression of Dicer1 was examined by immunohistochemistry in 276 NPC specimens, and the mRNA levels of Dicer1 were analyzed by qRT-PCR in 56 NPC and 11 nasopharyngitis tissues. Cox regression analysis was used to identify independent prognostic factors, and a prognostic score model was constructed for survival prediction. Expression of Dicer1 was downregulated in NPC tissues at both the mRNA and the protein levels, and there was a notable positive correlation between the expression levels of Dicer1 mRNA and protein. Low Dicer1 expression was positively correlated with distant metastasis (P < 0.01) and death (P = 0.01). In addition, low expression of Dicer1 was significantly associated with poorer overall survival (HR, 2.32; 95 % CI 1.30–4.14; P < 0.01) and poorer distant metastasis-free survival (HR, 2.56; 95 % CI 1.39–4.74; P < 0.01). Furthermore, multivariate analysis showed that low expression of Dicer1 and tumor-node-metastasis (TNM) stage was independent prognostic indicators for NPC patients. A prognostic score model combining the Dicer1 expression and TNM stage had a better prognostic value than the TNM stage alone model or Dicer1 expression alone model (P < 0.05). Dicer1 was downregulated in NPC tissues at both the mRNA and the protein levels, and low expression of Dicer1 could be served as novel prognostic biomarker for NPC patients.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Curado MP, Edwards BK. Cancer incidence in five continents. Vol IX. IARC Scientific Pub. No. 160. Lyon: IARC; 2007.

    Google Scholar 

  2. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.

    Article  PubMed  Google Scholar 

  3. Edge SB, Byrd DR. AJCC cancer staging manual. 7th ed. New York: Springer; 2010.

    Google Scholar 

  4. Au JS, Law CK, Foo W, Lau WH. In-depth evaluation of the AJCC/UICC 1997 staging system of nasopharyngeal carcinoma: prognostic homogeneity and proposed refinements. Int J Radiat Oncol Biol Phys. 2003;56:413–26.

    Article  PubMed  Google Scholar 

  5. Mao YP, Xie FY, Liu LZ, et al. Re-evaluation of 6th edition of AJCC staging system for nasopharyngeal carcinoma and proposed improvement based on magnetic resonance imaging. Int J Radiat Oncol Biol Phys. 2009;73:1326–34.

    Article  PubMed  Google Scholar 

  6. Leung SF, Zee B, Ma BB, et al. Plasma Epstein-Barr viral deoxyribonucleic acid quantitation complements tumor-node-metastasis staging prognostication in nasopharyngeal carcinoma. J Clin Oncol. 2006;24:5414–8.

    Article  PubMed  CAS  Google Scholar 

  7. Turen S, Ozyar E, Altundag K, Gullu I, Atahan IL. Serum lactate dehydrogenase level is a prognostic factor in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy. Cancer Invest. 2007;25:315–21.

    Article  PubMed  CAS  Google Scholar 

  8. Lv X, Xiang YQ, Cao SM, et al. Prospective validation of the prognostic value of elevated serum vascular endothelial growth factor in patients with nasopharyngeal carcinoma: more distant metastases and shorter overall survival after treatment. Head Neck. 2011;33:780–5.

    Article  PubMed  Google Scholar 

  9. Bernstein E, Caudy AA, Hammond SM, Hannon GJ. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature. 2001;409:363–6.

    Article  PubMed  CAS  Google Scholar 

  10. Hammond SM. Dicing and slicing: the core machinery of the RNA interference pathway. FEBS Lett. 2005;579:5822–9.

    Article  PubMed  CAS  Google Scholar 

  11. Merritt WM, Lin YG, Han LY, et al. Dicer1, Drosha, and outcomes in patients with ovarian cancer. N Engl J Med. 2008;359:2641–50.

    Article  PubMed  CAS  Google Scholar 

  12. Flavin RJ, Smyth PC, Finn SP, et al. Altered eIF6 and Dicer1 expression is associated with clinicopathological features in ovarian serous carcinoma patients. Mod Pathol. 2008;21:676–84.

    Article  PubMed  CAS  Google Scholar 

  13. Faggad A, Budczies J, Tchernitsa O, et al. Prognostic significance of Dicer1 expression in ovarian cancer-link to global microRNA changes and oestrogen receptor expression. J Pathol. 2010;220:382–91.

    PubMed  CAS  Google Scholar 

  14. Karube Y, Tanaka H, Osada H, et al. Reduced expression of Dicer1 associated with poor prognosis in lung cancer patients. Cancer Sci. 2005;96:111–5.

    Article  PubMed  CAS  Google Scholar 

  15. Chiosea S, Jelezcova E, Chandran U, et al. Overexpression of Dicer1 in precursor lesions of lung adenocarcinoma. Cancer Res. 2007;67:2345–50.

    Article  PubMed  CAS  Google Scholar 

  16. Sugito N, Ishiguro H, Kuwabara Y, et al. RNASEN regulates cell proliferation and affects survival in esophageal cancer patients. Clin Cancer Res. 2006;12:7322–8.

    Article  PubMed  CAS  Google Scholar 

  17. Chiosea S, Jelezcova E, Chandran U, et al. Up-regulation of Dicer1, a component of the MicroRNA machinery, in prostate adenocarcinoma. Am J Pathol. 2006;169:1812–20.

    Article  PubMed  CAS  Google Scholar 

  18. Grelier G, Voirin N, Ay AS, et al. Prognostic value of Dicer1 expression in human breast cancers and association with the mesenchymal phenotype. Br J Cancer. 2009;101:673–83.

    Article  PubMed  CAS  Google Scholar 

  19. Zighelboim I, Reinhart AJ, Gao F, et al. Dicer1 expression and outcomes in endometrioid endometrial adenocarcinoma. Cancer. 2011;117:1446–53.

    Article  PubMed  CAS  Google Scholar 

  20. Faber C, Horst D, Hlubek F, Kirchner T. Overexpression of Dicer1 predicts poor survival in colorectal cancer. Eur J Cancer. 2011;47:1414–9.

    Article  PubMed  CAS  Google Scholar 

  21. Ma J, Liu L, Tang L, et al. Retropharyngeal lymph node metastasis in nasopharyngeal carcinoma: prognostic value and staging categories. Clin Cancer Res. 2007;13:1445–52.

    Article  PubMed  CAS  Google Scholar 

  22. Chen Y, Liu MZ, Liang SB, et al. Preliminary results of a prospective randomized trial comparing concurrent chemoradiotherapy plus adjuvant chemotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma in endemic regions of china. Int J Radiat Oncol Biol Phys. 2008;71:1356–64.

    Article  PubMed  Google Scholar 

  23. Chan AT, Teo PM, Ngan RK, et al. Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial. J Clin Oncol. 2002;20:2038–44.

    Article  PubMed  CAS  Google Scholar 

  24. Li W, Yu CP, Xia JT, et al. Sphingosine kinase 1 is associated with gastric cancer progression and poor survival of patients. Clin Cancer Res. 2009;15:1393–9.

    Article  PubMed  CAS  Google Scholar 

  25. Liao WT, Wang X, Xu LH, et al. Centromere protein H is a novel prognostic marker for human nonsmall cell lung cancer progression and overall patient survival. Cancer. 2009;115:1507–17.

    Article  PubMed  CAS  Google Scholar 

  26. Korbler T, Grskovic M, Dominis M. Antica M (2004) A simple method for RNA isolation from formalin-fixed and paraffin-embedded lymphatic tissues. Exp Mol Pathol. 2003;74:336–40.

    Article  PubMed  CAS  Google Scholar 

  27. Marshall OJ. PerlPrimer: cross-platform, graphical primer design for standard, bisulphite and real-time PCR. Bioinformatics. 2004;20:2471–2.

    Article  PubMed  CAS  Google Scholar 

  28. Yang HI, Yuen MF, Chan HLY, et al. Risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B): development and validation of the predictive score. Lancet Oncol. 2011;12:568–74.

    Article  PubMed  Google Scholar 

  29. Liu N, Chen NY, Cui RX, et al. Prognostic value of a microRNA signature in nasopharyngeal carcinoma: a microRNA expression analysis. Lancet Oncol. 2012;13:633–41.

    Article  PubMed  CAS  Google Scholar 

  30. Sengupta S, Den Boon JA, Chen IH, et al. MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins. Proc Natl Acad Sci USA. 2008;105:5874–8.

    Article  PubMed  CAS  Google Scholar 

  31. Chen HC, Chen GH, Chen YH, et al. MicroRNA deregulation and pathway alterations in nasopharyngeal carcinoma. Br J Cancer. 2009;100:1002–11.

    Article  PubMed  CAS  Google Scholar 

  32. Cheng C, Fu X, Alves P, Gerstein M. mRNA expression profiles show differential regulatory effects of microRNAs between estrogen receptor-positive and estrogen receptor-negative breast cancer. Genome Biol. 2009;10:R90.

    Article  PubMed  Google Scholar 

  33. Guo X, Liao Q, Chen P, et al. The microRNA-processing enzymes: Drosha and Dicer1 can predict prognosis of nasopharyngeal carcinoma. J Cancer Res Clin Oncol. 2012;138:49–56.

    Article  PubMed  CAS  Google Scholar 

  34. Lai SZ, Li WF, Chen L, et al. How does intensity-modulated radiotherapy versus conventional two-dimensional radiotherapy influence the treatment results in nasopharyngeal carcinoma patients? Int J Radiat Oncol Biol Phys. 2011;80:661–8.

    Article  PubMed  Google Scholar 

  35. Hui EP, Leung SF, Au JS, et al. Lung metastasis alone in nasopharyngeal carcinoma: a relatively favorable prognostic group. A study by the Hong Kong Nasopharyngeal Carcinoma Study Group. Cancer. 2004;101:300–6.

    Article  PubMed  Google Scholar 

  36. Han L, Zhang A, Zhou X, et al. Downregulation of Dicer1 enhances tumor cell proliferation and invasion. Int J Oncol. 2010;37:299–305.

    PubMed  CAS  Google Scholar 

  37. Martello G, Rosato A, Ferrari F, et al. A MicroRNA targeting Dicer1 for metastasis control. Cell. 2010;141:1195–207.

    Article  PubMed  CAS  Google Scholar 

  38. Shao JY, Huang XM, Yu XJ, et al. Loss of heterozygosity and its correlation with clinical outcome and Epstein-Barr virus infection in nasopharyngeal carcinoma. Anticancer Res. 2001;21:3021–9.

    PubMed  CAS  Google Scholar 

  39. Cheng R, Lo K, Huang D, Tsao S. Loss of heterozygosity on chromosome 14 in primary nasopharyngeal carcinoma. Int J Oncol. 1997;10:1047–50.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the Science Foundation of the Key Hospital Clinical Program of the Ministry of Health, P.R. China (No. 2010-178), the National Natural Science Foundation of China (No. 81071835, 31170151), the Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2010), and the Key Scientific and Technological Innovation Program for Universities of Guangdong Province (No. cxzd1005).

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Hui-Yun Wang or Jun Ma.

Additional information

Na Liu and Rui-Xue Cui contributed equally to this article.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, N., Cui, RX., He, QM. et al. Reduced expression of Dicer11 is associated with poor prognosis in patients with nasopharyngeal carcinoma. Med Oncol 30, 360 (2013). https://doi.org/10.1007/s12032-012-0360-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-012-0360-3

Keywords

Navigation