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

Tumour Biol. 2013 Aug;34(4):2309-13. doi: 10.1007/s13277-013-0775-2. Epub 2013 Apr 9.

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.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Autoantigens / biosynthesis
  • Autoantigens / metabolism*
  • Biomarkers, Tumor / metabolism
  • Cadherins / biosynthesis
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Carcinoma, Pancreatic Ductal / mortality*
  • Carcinoma, Pancreatic Ductal / pathology
  • Epithelial-Mesenchymal Transition*
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Lymphatic Metastasis
  • Male
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Neoplasm Staging
  • Pancreas / metabolism
  • Pancreas / pathology
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / mortality*
  • Pancreatic Neoplasms / pathology
  • Prognosis
  • Survival
  • Survival Rate
  • Vimentin / biosynthesis

Substances

  • Autoantigens
  • Biomarkers, Tumor
  • CIP2A protein, human
  • Cadherins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Vimentin