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



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.


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


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.


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


Bevacizumab Nucleolus protein Novel VEGF isoform GBM Prognosis Mitogen 



Vascular endothelial growth factor A


Large VEGF


Reverse transcriptase-polymerase chain reaction


Heparin sulfate proteoglycans




U-87 MG cells


Matrix metalloproteinase


Glioblastoma multiforme


Messenger RNA



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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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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