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Prognostic Impacts of Angiopoietins in NSCLC Tumor Cells and Stroma: VEGF-A Impact Is Strongly Associated with Ang-2

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  • Sigve Andersen
  • Tom Donnem
  • Khalid Al-Shibli
  • Samer Al-Saad
  • Helge Stenvold
  • Lill-Tove Busund
  • Roy M Bremnes

Abstract

Introduction: Angiopoietins and their receptor Tie-2 are, in concert with VEGF-A, key mediators in angiogenesis. This study evaluates the prognostic impact of all known human angiopoietins (Ang-1, Ang-2 and Ang-4) and their receptor Tie-2, as well as their relation to the prognostic expression of VEGF-A. Methods: 335 unselected stage I-IIIA NSCLC-patients were included and tissue samples of respective tumor cells and stroma were collected in tissue microarrays (TMAs). Immunohistochemistry (IHC) was used to semiquantitatively evaluate the expression of markers in duplicate tumor and stroma cores. Principal Findings: In univariate analyses, low tumor cell expression of Ang-4 (P = 0.046) and low stromal expressions of Ang-4 (P = 0.009) and Ang-2 (P = 0.017) were individually associated with a poor survival. In the multivariate analysis, low stromal Ang-2 (HR 1.88; CI 95% 1.15-3.08) and Ang-4 (HR 1.47, CI 95% 1.02–2.11, P = 0.04) expressions were independently associated with a poor prognosis. In patients with high tumor cell expression of Ang-2, a concomitantly high tumor VEGF-A expression mediated a dramatic survival reduction (P

Suggested Citation

  • Sigve Andersen & Tom Donnem & Khalid Al-Shibli & Samer Al-Saad & Helge Stenvold & Lill-Tove Busund & Roy M Bremnes, 2011. "Prognostic Impacts of Angiopoietins in NSCLC Tumor Cells and Stroma: VEGF-A Impact Is Strongly Associated with Ang-2," PLOS ONE, Public Library of Science, vol. 6(5), pages 1-9, May.
    • Handle: RePEc:plo:pone00:0019773
    DOI: 10.1371/journal.pone.0019773
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    Cited by:

    1. Ling Lin & Kejian Cao & Wenhu Chen & Xufeng Pan & Heng Zhao, 2013. "Four Common Vascular Endothelial Growth Factor Polymorphisms (−2578C>A, −460C>T, +936C>T, and +405G>C) in Susceptibility to Lung Cancer: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 8(10), pages 1-12, October.

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