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

Shao-Wei Feng,Ying Chen,Dueng-Yuan Hueng,Yun-Ju Yang,Chih-Chuan Hsieh,Wen-Chiuan Tsai,Hsin-Ying Clair Chiou,Chin Lin,Li-Chun Huang,Sheng-Tang Wu

doi:10.18632/oncotarget.10021

Shao-Wei Feng, Ying Chen + Show 8 more

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https://doi.org/10.18632/oncotarget.10021

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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 × 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.

Highlights

World Health Organization (WHO) grade III anaplastic astrocytoma, and grade IV glioblastoma multiforme (GBM) are defined as high-grade gliomas with poor survival outcome [1, 2]
This study showed that high Telomere maintenance 2 (TELO2) mRNA expression predicts poor survival outcome in comparison with low TELO2 mRNA expression
TELO2 expression was significantly greater in patients with highgrade gliomas than in low-grade gliomas and in those with non-tumor brain controls

Summary

Introduction

World Health Organization (WHO) grade III anaplastic astrocytoma, and grade IV glioblastoma multiforme (GBM) are defined as high-grade gliomas with poor survival outcome [1, 2]. High-grade gliomas still progressed and recurred despite of aggressive therapies [3]. Biomarker for distinguishing clinical outcome is urgently needed in high-grade gliomas to provide oncotarget for clinician to improve the clinical outcome [4, 5]. Telomere maintenance 2 (TELO2) was first found in Saccharomyces cerevisiae to regulate the telomere www.impactjournals.com/oncotarget length [6]. TELO2 was found in Caenorhabditis elegans to control biological rhythms and life span and named CLK2 [7, 8]. Studies showed TEL2/CLK2 orthologs increased the telomere length in Caenorhabditis elegans and the budding yeast Saccharomyces cerevisiae [12,13,14,15]

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