CIP2A is a predictor of poor prognosis in colon cancer

J Gastrointest Surg. 2012 May;16(5):1037-47. doi: 10.1007/s11605-012-1828-3. Epub 2012 Feb 11.


Purpose: The cancerous inhibitor of protein phosphatase 2A (CIP2A) oncoprotein is overexpressed in colon cancer tissue compared to normal colon mucosa. We investigated the impact of CIP2A on colon cancer.

Methods: A tissue microarray consisting of 167 colon cancer specimens was investigated. The association between CIP2A and clinicopathological parameters was analyzed using the χ(2) test. Survival was analyzed using the Kaplan-Meier method. The impact of CIP2A on proliferation and drug resistance was evaluated using the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide test. An anchorage-independent colony formation assay was also performed.

Results: CIP2A was an independent prognostic factor in colon cancer after controlling for other clinical confounding factors, such as stage and lymphovascular invasion, particularly in stages III and IV (hazard ratio = 2.974, P < 0.001). The knockdown of CIP2A reduced the proliferation and anchorage-independent colony formation of colon cancer cells. Knockdown of CIP2A decreased the resistance of the cells to 5-fluorouracil, oxaliplatin, and SN38 (an active metabolite of irinotecan). Treatment with 5-fluorouracil, oxaliplatin, and SN38 decreased CIP2A expression.

Conclusions: CIP2A is a prognostic factor in colon cancer. The knockdown of CIP2A reduced proliferation and anchorage-independent colony formation and increased 5-fluorouracil, oxaliplatin, and SN38 efficacy in colon cancer cell lines.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology
  • Autoantigens / drug effects
  • Autoantigens / genetics
  • Autoantigens / metabolism*
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism
  • Biopsy, Needle
  • Blotting, Western
  • Cell Proliferation / drug effects
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / mortality*
  • Colonic Neoplasms / pathology*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins
  • Kaplan-Meier Estimate
  • Male
  • Membrane Proteins / drug effects
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Protein Array Analysis / methods
  • RNA, Neoplasm / metabolism
  • Real-Time Polymerase Chain Reaction / methods
  • Risk Assessment
  • Survival Analysis
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • Autoantigens
  • Biomarkers, Tumor
  • CIP2A protein, human
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • RNA, Neoplasm