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

Abstract

PURPOSE:

Vascular endothelial growth factor (VEGF) is a potent mediator of vascular permeability. VEGF inhibition reduces edema and tumor burden in some patients with malignant glioma, whereas others show no response. The role of VEGF expression in edema production and the relationship to survival is not well understood.

EXPERIMENTAL DESIGN:

Using DNA microarray analysis, we examined VEGF and related gene expression in 71 newly diagnosed malignant gliomas and analyzed the relationship to edema and survival.

RESULTS AND CONCLUSIONS:

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.

• Authors: Marc R J Carlson, Whitney B Pope, Steve Horvath, Jerome G Braunstein, Phioanh Nghiemphu, Cho-Lea Tso, Ingo Mellinghoff, Albert Lai, Linda M Liau, Paul S Mischel, Jun Dong, Stanley F Nelson, Timothy F Cloughesy
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 13 Issue 9 Pg. 2592-8 (May 01 2007) ISSN: 1078-0432 [Print] United States
• PMID: 17473188 (Publication Type: Journal Article)

Chemical References

• Angiopoietin-2
• Hypoxia-Inducible Factor 1, alpha Subunit
• Nerve Tissue Proteins
• Vascular Endothelial Growth Factor A
• neuronal pentraxin
• Adrenomedullin
• Aquaporin 3
• C-Reactive Protein

Topics

• Adrenomedullin (genetics)
• Angiopoietin-2 (genetics)
• Aquaporin 3 (genetics)
• Brain Edema (diagnosis, genetics)
• Brain Neoplasms (complications, mortality)
• C-Reactive Protein (genetics)
• Gene Expression
• Glioma (complications, mortality)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (genetics)
• Nerve Tissue Proteins (genetics)
• Oligonucleotide Array Sequence Analysis
• Prognosis
• Survival
• Vascular Endothelial Growth Factor A (genetics)