The expression of both peroxisome proliferator-activated receptor delta and cyclooxygenase-2 in tissues is associated with poor prognosis in colorectal cancer patients

Dig Dis Sci. 2011 Apr;56(4):1194-200. doi: 10.1007/s10620-010-1389-9. Epub 2010 Sep 8.

Abstract

Background: The role of peroxisome proliferator-activated receptor delta (PPAR δ) in the development and progression of colorectal cancer (CRC) remains controversial.

Aims: We investigated the impact of PPAR δ expression in tissues on liver metastasis of CRC.

Methods: We analyzed samples of primary CRC and matched normal adjacent tissues from 52 patients for the expression of PPAR δ, cyclooxygenase (COX)-2, vascular endothelial growth factor (VEGF)-A, and CXC chemokine receptor 4 (CXCR4). Correlations of the molecules expressions with clinical characteristics and prognosis of patients were studied.

Results: The number of patients positive for PPAR δ, COX-2, CXCR4, and VEGF-A was 25, 33, 18, and 19, respectively. Among the PPAR δ (+)/COX-2 (+), PPAR δ (-)/COX-2 (+), PPAR δ (+)/COX-2 (-), and PPAR δ (-)/COX-2 (-) patient groups, PPAR δ (+)/COX-2 (+) patients had the highest incidence of liver metastasis (p<0.01). PPAR δ (+)/COX-2 (+) expression was a significant independent prognostic factor (HR=7.108, 95% CI 1.231-41.029, p=0.0283) by Cox proportional analysis. PPAR δ (+)/COX-2 (+) patients had the highest positivity for CXCR4 or VEGF-A in tissues (p<0.01). Among the patients in the CXCR4 (+)/VEGF-A (+), CXCR4 (+)/VEGF-A (-), CXCR4 (-)/VEGF-A (+), and CXCR4 (-)/VEGF-A (-) groups, CXCR4 (+)/VEGF-A (+) patients had the highest incidence of liver metastasis (p<0.01).

Conclusions: The expression of both PPAR δ and COX-2 in tissues may lead to liver metastasis and consequent poor prognosis in CRC patients.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma / metabolism
  • Carcinoma / secondary*
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology*
  • Cyclooxygenase 2 / biosynthesis*
  • Female
  • Humans
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / secondary*
  • Male
  • Middle Aged
  • PPAR delta / biosynthesis*
  • Prognosis
  • Receptors, CXCR4 / biosynthesis
  • Vascular Endothelial Growth Factor A / biosynthesis

Substances

  • CXCR4 protein, human
  • PPAR delta
  • Receptors, CXCR4
  • Vascular Endothelial Growth Factor A
  • Cyclooxygenase 2