Prognostic Impact of COX-2 in Non-Small Cell Lung Cancer: A Comprehensive Compartment-Specific Evaluation of Tumor and Stromal Cell Expression

Cancer Lett. 2015 Jan 28;356(2 Pt B):837-45. doi: 10.1016/j.canlet.2014.10.032. Epub 2014 Oct 31.

Abstract

Cyclooxygenase-2 (COX-2) is an enzyme that has been extensively investigated as a prognostic marker in cancer. In non-small cell lung cancer (NSCLC) previous results regarding the prognostic impact of COX-2 expression are inconsistent. Therefore we evaluated the association between transcript levels and overall survival in nine publicly available gene expression data sets (total n = 1337) and determined in situ compartment-specific tumor and stromal cell protein expression in two independent cohorts (n = 616). Gene expression did not show any correlation with clinical parameters or with overall survival. Protein expression in tumor and stromal cells did not correlate with any clinical parameter or with overall survival in one of the analyzed cohorts, while a significant association of high stromal expression with longer survival was observed in both univariate and multivariate analysis in the other cohort. Stromal expression of COX-2 has not been separately evaluated in NSCLC previously and may be a subject of further investigation, whereas the presented findings from this comprehensive compartment specific evaluation clearly reject the hypothesis of COX-2 tumor cell expression having a prognostic value in NSCLC.

Keywords: Cyclooxygenase 2; Immunohistochemistry; Lung cancer; Microarray; PTGS2; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Large Cell / metabolism
  • Carcinoma, Large Cell / mortality
  • Carcinoma, Large Cell / pathology
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Cohort Studies
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism*
  • Female
  • Humans
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stromal Cells / metabolism*
  • Stromal Cells / pathology

Substances

  • Biomarkers, Tumor
  • RNA, Messenger
  • Cyclooxygenase 2
  • PTGS2 protein, human