Overexpression of TELO2 decreases survival in human high-grade gliomas
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Shao-Wei Feng1, Ying Chen2, Wen-Chiuan Tsai3, Hsin-Ying Clair Chiou1, Sheng-Tang Wu4, Li-Chun Huang5, Chin Lin6, Chih-Chuan Hsieh1, Yun-Ju Yang1, Dueng-Yuan Hueng1,5,7
1Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.
2Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan, R.O.C.
3Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.
4Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.
5Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, R.O.C.
6Graduate Institute of Life Science, National Defense Medical Center, Taipei, Taiwan, R.O.C.
7Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan, R.O.C.
Dueng-Yuan Hueng, email: email@example.com
Keywords: gliomas, WHO grades, GEO profile, Telomere maintenance 2, TELO2
Received: September 26, 2015 Accepted: May 28, 2016 Published: June 14, 2016
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.
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