The Prognostic Significance of Combining VEGFA, FLT1 and KDR mRNA Expressions in Brain Tumors

Abstract

Tumor cells require angiogenesis to deliver nutrients and oxygen to support their fast growth and metabolism. The vascular endothelial growth factor (VEGF) pathway plays an important role in promoting angiogenesis, including tumor-induced angiogenesis. Recent clinical trials have demonstrated the benefit of targeting VEGF in the treatment of glioblastoma. However, the prognostic significance of the expression of VEGFA and its receptors VEGFR1 (FLT1) and VEGFR2 (KDR) are still largely elusive. In the present study, we aimed to investigate the prognostic significance of these three factors, alone or in combination, in glioma patients. Gene mRNA expression was extracted from three independent brain tumor cohorts totaling 242 patients and the association between gene expression and survival was tested. We found that when VEGFA, FLT1 and KDR expressions were considered alone, only VEGFA demonstrated a significant association with patient survival. Patients with high expression of both VEGFA and either receptor had significantly worse survival than patients expressing both factors at a low level. Importantly, we found that those patients whose tumors overexpressed all three genes had a significantly shorter survival compared to those patients with a low level expression of these genes. Our results suggest that a high level expression of VEGFA and its receptors, both FLT1 and KDR, may be required for brain tumor progression, and that these three factors should be considered together as a prognostic indicator for brain tumor patients.

A Dexamethasone-regulated Gene Signature Is Prognostic for Poor Survival in Glioblastoma Patients

“…34 VEGFA, one of five VEGF subtypes, has been shown to be a prognostic indicator for brain tumor patients. 35 Given that vascular proliferation is a key component of glioblastoma biology and that VEGF expression levels directly correlate with tumor malignancy and hence inversely with prognosis, the anti-VEGF antibody bevacizumab has been approved by the FDA for treatment of recurrent glioblastoma. 36, 37 The role of estrogen receptors in glioblastoma remains controversial: some evidence shows that estrogen receptors are decreased in high-grade gliomas, while estrogen receptor expression levels correlated negatively with tumor differentiation.…”

Open Data for Differential Network Analysis in Glioma

“…ANXA1 is also known to be involved in proliferation, differentiation and apoptosis, serves as a substrate for EGFR, and is implicated in tumor progression of astrocytoma [65]. VEGFA is involved in promoting tumor-induced angiogenesis and implicated with brain tumor progression [66]. Transforming growth factor receptor beta (TGFB) is likewise involved in the regulation of cell proliferation and postulated as a target for glioma therapy [67].…”

MicroRNA-140-5p inhibits cell proliferation and invasion by regulating VEGFA/MMP2 signaling in glioma

“…17 Activation of downstream signaling pathways promotes endothelial cell proliferation, angiogenesis, and glioma cell growth. 16 By contrast, matrix metalloproteinases (MMPs) are a family of zinc-dependent enzymes that are secreted in an inactive precursor form. The proenzyme form of MMP is activated autocatalytically or by other contributing proteinases.…”

“…13 Moreover, VEGF plays a central role in glioma progression, especially in the context of glioma stem cells. [14][15][16] VEGFA is an important member of the VEGF family and includes VEGFA, VEGFB, VEGFC, VEGFD, and placental growth factor (PIGF).…”