Skip to main content

Advertisement

SpringerLink
Log in

CIP2A expression is associated with altered expression of epithelial–mesenchymal transition markers and predictive of poor prognosis in pancreatic ductal adenocarcinoma

  • Research Article
  • Published:
Tumor Biology

Abstract

CIP2A has been regarded as a novel potential therapeutic target for multiple cancers. The aim of this study was to detect CIP2A expression in pancreatic ductal adenocarcinoma (PDA) and to analyze its association with prognosis of PDA patients. The expression of CIP2A and three epithelial–mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin, and vimentin) was examined in 96 PDA tissue samples by immunohistochemistry. Fifty-four cases (56.3 %) were defined as positive for CIP2A expression. Immunohistochemistry showed that CIP2A expression was correlated with poor tumor differentiation, TNM stage, and lymph node metastasis. Kaplan–Meier survival analysis showed that patients with CIP2A-positive expression showed lower overall survival rate than those with CIP2A-negative expression. Multivariate analysis showed that CIP2A expression was an independent prognostic factor for PDA patients. Furthermore, positive expression of CIP2A was strongly associated with loss of the epithelial marker E-cadherin and acquisition of the expression of the mesenchymal markers N-cadherin and vimentin. These findings suggest that CIP2A might promote EMT and progression in PDA, and thus may be a potential therapeutic target for patients with PDA.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Hingorani SR. Location, location, location: precursors and prognoses for pancreatic cancer. Gastroenterology. 2007;133:345–50.

    Article  PubMed  Google Scholar 

  2. Lockhart AC, Rothenberg ML, Berlin JD. Treatment for pancreatic cancer: current therapy and continued progress. Gastroenterology. 2005;128:1642–54.

    Article  PubMed  CAS  Google Scholar 

  3. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300. doi:10.3322/caac.20073.

    Article  PubMed  Google Scholar 

  4. Sharma C, Eltawil KM, Renfrew PD, Walsh MJ, Molinari M. Advances in diagnosis, treatment and palliation of pancreatic carcinoma: 1990–2010. World J Gastroenterol. 2011;17:867–97. doi:10.3748/wjg.v17.i7.867.

    Article  PubMed  Google Scholar 

  5. Farrow B, Berger DH, Rowley D. Tumor-derived pancreatic stellate cells promote pancreatic cancer cell invasion through release of thrombospondin-2. J Surg Res. 2009;156:155–60. doi:10.1016/j.jss.2009.03.040.

    Article  PubMed  CAS  Google Scholar 

  6. Junttila MR, Puustinen P, Niemelä M, Ahola R, Arnold H, Böttzauw T, et al. CIP2A inhibits PP2A in human malignancies. Cell. 2007;130:51–62.

    Article  PubMed  CAS  Google Scholar 

  7. Basile JR, Czerninski R. The role of CIP2A in oral squamous cell carcinoma. Cancer Biol Ther. 2010;10:700–2. doi:10.4161/cbt.10.7.13151.

    Article  PubMed  CAS  Google Scholar 

  8. Côme C, Laine A, Chanrion M, Edgren H, Mattila E, Liu X, et al. CIP2A is associated with human breast cancer aggressivity. Clin Cancer Res. 2009;15:5092–100. doi:10.1158/1078-0432.CCR-08-3283.

    Article  PubMed  Google Scholar 

  9. Huang LP, Adelson ME, Mordechai E, Trama JP. CIP2A expression is elevated in cervical cancer. Cancer Biomark. 2010–2011;8:309–17. doi: 10.3233/CBM-2011-0220

    Google Scholar 

  10. Li W, Ge Z, Liu C, Liu Z, Björkholm M, Jia J, et al. CIP2A is overexpressed in gastric cancer and its depletion leads to impaired clonogenicity, senescence, or differentiation of tumor cells. Clin Cancer Res. 2008;14:3722–8. doi:10.1158/1078-0432.CCR-07-4137.

    Article  PubMed  CAS  Google Scholar 

  11. Vaarala MH, Väisänen MR, Ristimäki A. CIP2A expression is increased in prostate cancer. J Exp Clin Cancer Res. 2010;29:136. doi:10.1186/1756-9966-29-136.

    Article  PubMed  Google Scholar 

  12. Huang LP, Savoly D, Sidi AA, Adelson ME, Mordechai E, Trama JP. CIP2A protein expression in high-grade, high-stage bladder cancer. Cancer Med. 2012;1(1):76–81. doi:10.1002/cam4.15.

    Article  PubMed  CAS  Google Scholar 

  13. Xue Y, Wu G, Wang X, Zou X, Zhang G, Xiao R, et al. CIP2A is a predictor of survival and a novel therapeutic target in bladder urothelial cell carcinoma. Med Oncol. 2013;30(1):406. doi:10.1007/s12032-012-0406-6.

    Article  PubMed  Google Scholar 

  14. He H, Wu G, Li W, Cao Y, Liu Y. CIP2A is highly expressed in hepatocellular carcinoma and predicts poor prognosis. Diagn Mol Pathol. 2012;21:143–9. doi:10.1097/PDM.0b013e318249fd8b.

    Article  PubMed  CAS  Google Scholar 

  15. Ren J, Li W, Yan L, Jiao W, Tian S, Li D, et al. Expression of CIP2A in renal cell carcinomas correlates with tumour invasion, metastasis and patients' survival. Br J Cancer. 2011;105:1905–11. doi:10.1038/bjc.2011.492.

    Article  PubMed  CAS  Google Scholar 

  16. Sobin LH, Wittekind CH. TNM classification of malignant tumours. 6th ed. New York: Wiley-Liss; 2002. p. 199–202.

    Google Scholar 

  17. Kelly K, Crowley J, Bunn Jr PA, Presant CA, Grevstad PK, Moinpour CM, et al. Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non-small-cell lung cancer: a Southwest Oncology Group trial. J Clin Oncol. 2001;19:3210–8.

    PubMed  CAS  Google Scholar 

  18. Hennessy BT, Hanrahan EO, Daly PA. Non-Hodgkin lymphoma: an update. Lancet Oncol. 2004;5:341–53.

    Article  PubMed  Google Scholar 

Download references

Conflicts of interest

None

Author information

Authors and Affiliations

  1. Department of General Surgery, First People’s Hospital of Changshu City, Changshu Hospital Affiliated to Soochow University, No. 1 Shuyuan Rd, Changshu, 215500, Jiangsu Province, China

    Lei Wang & Feng Gu

  2. Department of General Surgery, Nanjing Hospital Affiliated to Nanjing Medical University, No. 68 Changle Rd, Nanjing, 210006, Jiangsu Province, China

    Ning Ma, Lei Zhang, Jian-Min Bian & Hong-Yong Cao

Authors
  1. Lei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Feng Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ning Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jian-Min Bian
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hong-Yong Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hong-Yong Cao.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, L., Gu, F., Ma, N. et al. CIP2A expression is associated with altered expression of epithelial–mesenchymal transition markers and predictive of poor prognosis in pancreatic ductal adenocarcinoma. Tumor Biol. 34, 2309–2313 (2013). https://doi.org/10.1007/s13277-013-0775-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-013-0775-2

Keywords

Search

Navigation