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Journal of Neuro-Oncology

, Volume 140, Issue 1, pp 37–47 | Cite as

High expression of a novel splicing variant of VEGF, L-VEGF144 in glioblastoma multiforme is associated with a poorer prognosis in bevacizumab treatment

  • Wen-Yu Cheng
  • Chiung-Chyi Shen
  • Ming-Tsang Chiao
  • Yea-Jiuan Liang
  • Tsuo-Fei Mao
  • Bai-Shuan Liu
  • Jun-Peng Chen
Clinical Study

Abstract

Introduction

A previous study confirmed that a novel splicing variant of large vascular endothelial growth factor (L-VEGF) termed L-VEGF144, a nucleolus protein, is found in glioblastoma cells and specimens, but the actual biological function and clinical significance of L-VEGF144 remain unclear.

Methods

In this study, we analyzed the expression of L-VEGF144 in 68 glioblastoma multiforme specimens using reverse transcriptase-polymerase chain reaction analysis.

Results

The results showed that the high expression of L-VEGF144 was associated with a poor prognosis in the bevacizumab plus concurrent chemoradiotherapy with temozolomide treatment. In addition, we constructed a series truncated and mutant form of L-VEGF144 to confirm that exon 6a of L-VEGF144 is able to engage in the nuclear importation and found that 8 lysines within exon 6a play a critical role in the nucleolus aggregation of L-VEGF144. Also, the transfection of the L-VEGF144 increased the number of nucleoli. Furthermore, the recombinant protein Flag-L-VEGF144 and commercial VEGF protein have similar growth stimulatory activities in terms of inducing glioblastoma cell proliferation in vitro.

Conclusions

Taken together, these results indicated that the expression of L-VEGF144 could potentially serve as an independent indicator of poor prognosis in bevacizumab treatment.

Keywords

Bevacizumab Nucleolus protein Novel VEGF isoform GBM Prognosis Mitogen 

Abbreviations

VEGF

Vascular endothelial growth factor A

L-VEGF

Large VEGF

RT-PCR

Reverse transcriptase-polymerase chain reaction

HSPGs

Heparin sulfate proteoglycans

NRP1

Neuropilin-1

U87

U-87 MG cells

MMP

Matrix metalloproteinase

GBM

Glioblastoma multiforme

mRNA

Messenger RNA

Notes

Acknowledgements

We appreciated Prof Dr. Shih-Lan Hsu (Department of Medical Research, Taichung Veterans General Hospital) for providing valuable suggestions. This study was supported by grants from Taichung Veterans General Hospital; Grant Numbers: TCVGH-CTUST 10577011, TCVGH-1054904C, TCVGH-1064904C, TCVGH-YM1060206, TCVGH-10549038, Taiwan.

Compliance with ethical standards

Conflict of interest

No potential conflicts of interest were disclosed.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Minimally Invasive Neurosurgery, Neurological InstituteTaichung Veterans General HospitalTaichungTaiwan, ROC
  2. 2.Department of Physical TherapyHung Kuang UniversityTaichungTaiwan, ROC
  3. 3.Department of MedicineNational Defense Medical CenterTaipeiTaiwan, ROC
  4. 4.Tri-Service General HospitalNational Defense Medical CenterTaipeiTaiwan, ROC
  5. 5.Department of Game and Product DesignChienkuo Technology UniversityChanghuaTaiwan, ROC
  6. 6.Department of Medical Imaging and Radiological SciencesCentral Taiwan, ROC University of Science and TechnologyTaichungTaiwan, ROC
  7. 7.Biostatistics Task Force of Taichung Veterans General HospitalTaichungTaiwan, ROC

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