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Oncotarget. 2016 Jul 19;7(29):46056-46066. doi: 10.18632/oncotarget.10021.

Overexpression of TELO2 decreases survival in human high-grade gliomas.

Author information

1
Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.
2
Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan, R.O.C.
3
Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.
4
Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.
5
Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, R.O.C.
6
Graduate Institute of Life Science, National Defense Medical Center, Taipei, Taiwan, R.O.C.
7
Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan, R.O.C.

Abstract

High-grade gliomas are characterized with poor prognosis. To improve the clinical outcome, biomarker is urgently needed for distinguishing oncotarget in high-grade gliomas. Telomere maintenance 2 (TELO2) regulates S-phase checkpoint in cell cycle, and is involved in DNA repair. However, the role of TELO2 in survival outcome of high-grade gliomas is still not yet clarified. This study aims to investigate the correlation between TELO2 mRNA expression and survival outcome of patients with high-grade gliomas. Based on bioinformatics study, we found that Kaplan-Meier analysis demonstrated shorter survival in patients with higher TELO2 mRNA levels than in those with lower TELO2 expression (median survival, 59 vs. 113 weeks, p=0.0017, by log-rank test, hazard ratio: 0.3505, 95% CI: 01824.-0.6735). TELO2 mRNA expression significantly higher in World Health Organization (WHO) grade IV than in non-tumor control (p=2.85 x 10-9). Moreover, TELO2 level was greater in WHO grade III than in non-tumor controls (p= 0.017) human gliomas. We further validated TELO2 mRNA expression and protein levels by using quantitative RT-PCR, Western blot, and immunohistochemical (IHC) stain of tissue microarray. Consistently, the TELO2 mRNA and protein expression were significantly elevated in human glioma cells in comparison with normal brain control. Additionally, IHC staining showed higher TELO2 immunostain score in high-grade gliomas than in low-grade gliomas, or normal brain control. Taken together, human high-grade gliomas increase TELO2 mRNA expression, and overexpression of TELO2 mRNA expression correlates with shorter survival outcome, supporting that TELO2 is an oncotarget in human gliomas.

KEYWORDS:

GEO profile; TELO2; Telomere maintenance 2; WHO grades; gliomas

PMID:
27329594
PMCID:
PMC5216781
DOI:
10.18632/oncotarget.10021
[Indexed for MEDLINE]
Free PMC Article

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