Prognostic significance of COX-2 immunohistochemical expression in colorectal cancer: a meta-analysis of the literature

PLoS One. 2013;8(3):e58891. doi: 10.1371/journal.pone.0058891. Epub 2013 Mar 20.


Background: Cyclooxygenase-2 (COX-2) is believed to be an important enzyme in the pathogenesis of colorectal cancer (CRC). Correlations between the expression of COX-2 with tumor growth and distant metastasis have become an issue; thus, attention has been paid to COX-2 as a prognostic factor. Various studies examined the relationship between COX-2 immunohistochemistry (IHC) overexpression with the clinical outcome in patients with colorectal cancer, but yielded conflicting results. The prognostic significance of COX-2 overexpression in colorectal cancer remains controversial.

Methods: Electronic databases updated to October 2012 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between COX-2 overexpression and survival of patients with colorectal cancer. Survival data were aggregated and quantitatively analyzed.

Results: We performed a meta-analysis of 23 studies (n = 4567 patients) that evaluated the correlation between COX-2 overexpression detected by IHC and survival in patients with colorectal cancer. Combined hazard ratios suggested that COX-2 overexpression had an unfavorable impact on overall survival (OS) (HR [hazard ratio] = 1.193, 95% CI [confidence interval]: 1.02 ∼ 1.37), but not disease free survival (DFS) (HR = 1.25, 95% CI: 0.99 ∼ 1.50) in patients with colorectal cancer.

Conclusions: Cox-2 overexpression in colorectal cancer detected by IHC appears to have slightly worse overall survival. However, the prognostic value of COX-2 on survival in colorectal cancer still needs further large-scale prospective trials to be clarified.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / mortality
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism*
  • Gene Expression
  • Genetic Association Studies
  • Humans
  • Immunohistochemistry
  • Prognosis
  • Publication Bias


  • Cyclooxygenase 2

Grant support

This study was supported by a grant from Medical Science Research Foundation of Health Bureau of Zhejiang Province (Grant number: 2012KYA072) and a grant from Administration of Traditional Chinese Medicine of Zhejiang Province (Grant number: 2012ZB084). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.