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Relationship between survival and edema in malignant gliomas: role of vascular endothelial growth factor and neuronal pentraxin 2.

Authors
  • Carlson, Marc R J
  • Pope, Whitney B
  • Horvath, Steve
  • Braunstein, Jerome G
  • Nghiemphu, Phioanh
  • Tso, Cho-Lea
  • Mellinghoff, Ingo
  • Lai, Albert
  • Liau, Linda M
  • Mischel, Paul S
  • Dong, Jun
  • Nelson, Stanley F
  • Cloughesy, Timothy F
Type
Published Article
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
Publication Date
May 01, 2007
Volume
13
Issue
9
Pages
2592–2598
Identifiers
PMID: 17473188
Source
Medline
License
Unknown

Abstract

VEGF expression was predictive of survival in tumors with little or no edema [Cox proportional hazard model, 6.88; 95% confidence interval (95% CI), 2.61-18.1; P<0.0001], but not in tumors with extensive edema. The expression of several proangiogenic genes, including adrenomedullin (correlation coefficient, 0.80), hypoxia-inducible factor-1A (0.51), and angiopoietin-2 (0.44), was correlated with VEGF expression (all with P<0.0001), whereas that of several antiangiogenic genes was inversely correlated. The expression of six genes was increased greater than 3-fold in edematous versus nonedematous tumors in the absence of increased VEGF expression. The most increased, neuronal pentraxin 2 (NPTX2, 7-fold change), was predictive of survival in tumors with the highest levels of edema, in contrast to VEGF (hazard ratio, 2.73; 95% CI, 1.49-5.02; P=0.049). NPTX2 was tightly correlated with expression of the water channel aquaporin-3 (0.74, P<0.0001). These results suggest that there are both VEGF-dependent and VEGF-independent pathways of edema production in gliomas and may explain why edema is not reduced in some patients following anti-VEGF treatment.

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