Co-overexpression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 adversely affects the postoperative survival in non-small cell lung cancer

J Thorac Oncol. 2010 Aug;5(8):1167-74. doi: 10.1097/JTO.0b013e3181e2f4f5.

Abstract

Introduction: Cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES)-1 have been found to be overexpressed in non-small cell lung cancer (NSCLC). The aim of this study was to investigate the expression profiles of COX-2 and mPGES-1 and their correlation with the clinical characteristics and survival outcomes in patients with resected NSCLC.

Methods/results: Seventy-nine paired adjacent normal-tumor matched samples were prospectively procured from patients undergoing surgery for NSCLC. The protein levels of COX-2 and mPGES-1 were assessed by Western blot analysis. Overexpression in the tumor sample was defined as more than twofold increase in protein expression compared with the corresponding adjacent normal tissue. Co-overexpression of COX-2 and mPGES-1 were further confirmed by immunohistochemistry. COX-2 was overexpressed in 58% and mPGES-1 in 70% of the tumor samples (p < 0.0001). Co-overexpression of mPGES-1 and COX-2 was noted in 43%, and they were unrelated to each other (p = 0.232). Co-overexpression of both proteins was significantly associated with less tumor differentiation (p = 0.046), tumor size larger than 5 cm (p = 0.038), and worse survival status during the follow-up (p = 0.036). Multivariate analysis showed that in addition to overall stage, co-overexpression of both proteins adversely affected the overall (hazard ratio, 2.40; p = 0.045) and disease-free survivals (hazard ratio, 2.27; p = 0.029).

Conclusions: Overexpression of either COX-2 or mPGES-1 is common but unrelated in NSCLC. Co-overexpression of both COX-2 and mPGES-1 adversely affects postoperative overall and disease-free survivals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Blotting, Western
  • Carcinoma, Large Cell / metabolism*
  • Carcinoma, Large Cell / mortality
  • Carcinoma, Large Cell / surgery
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Cyclooxygenase 2 / metabolism*
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Intramolecular Oxidoreductases / metabolism*
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Neoplasms, Squamous Cell / metabolism*
  • Neoplasms, Squamous Cell / mortality
  • Neoplasms, Squamous Cell / surgery
  • Prognosis
  • Prospective Studies
  • Prostaglandin-E Synthases
  • Survival Rate

Substances

  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Intramolecular Oxidoreductases
  • PTGES protein, human
  • Prostaglandin-E Synthases