Brain Tumor Pathology

, Volume 31, Issue 1, pp 1–10 | Cite as

Relationship of 14-3-3zeta (ζ), HIF-1α, and VEGF expression in human brain gliomas

  • Wei-Dong Cao
  • Nobuyuki KawaiEmail author
  • Keisuke Miyake
  • Xiang ZhangEmail author
  • Zhou Fei
  • Takashi Tamiya
Original Article


Accumulating evidence suggests that tissue hypoxia and apoptosis play important roles in the malignant progression of brain tumors. We investigated the relationship of 14-3-3zeta (an apoptosis-related protein), HIF-1α, and VEGF immunohistochemistry, and evaluated the prognostic value of their expression in human brain gliomas. A semiquantitative analysis of the immunoreactivity scores (IRSs) of the 14-3-3zeta, HIF-1α, and VEGF proteins was performed in 27 patients with various grades of gliomas. The IRS of 14-3-3zeta increased with tumor grade, with grade IV gliomas having the highest score (P < 0.05). Similar results were found for the IRSs of HIF-1α and VEGF (P < 0.05). A significant positive correlation was found between the IRSs of 14-3-3zeta and HIF-1α, 14-3-3zeta and VEGF, and HIF-1α and VEGF (P < 0.001 for all). The survival time of HIF-1α in grade III and grade IV glioma patients with low IRSs (0–6) was significantly longer than that in such glioma patients with high IRSs (8–12) (P < 0.05). These data indicate that 14-3-3zeta, HIF-1α, and VEGF are involved in the same cascade of the malignant progression of gliomas. Further studies will elucidate their detailed role in the malignant progression of glioma, and will contribute to the development of a new treatment strategy for this lethal disease.


Glioma 14-3-3zeta HIF-1α VEGF 



This study was supported by Grants-in-Aid for Scientific Research (C) (21591845) and (B) (22390277) from the Ministry of Education, Science and Culture of Japan. Wei-Dong Cao is a research doctor from the Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, China. This study was also supported by a Grant in China (National Nature Science Foundation of China, no: 81072083).

Conflict of interest

The authors have no conflict of interest.


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Copyright information

© The Japan Society of Brain Tumor Pathology 2013

Authors and Affiliations

  1. 1.Department of Neurological Surgery, Faculty of MedicineKagawa UniversityMiki-cho, Kita-gunJapan
  2. 2.Department of Neurosurgery, Xijing HospitalFourth Military Medical UniversityXi’anChina

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