Overexpression of TELO2 decreases survival in human high-grade gliomas.
Overexpression of TELO2 decreases survival in human high-grade gliomas.
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DOI：
10.18632/oncotarget.10021
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发表时间：
2016-07-19
期刊：
影响因子：
--
通讯作者：
Hueng DY
中科院分区：
文献类型：
--
作者：
Feng SW;Chen Y;Tsai WC;Chiou HC;Wu ST;Huang LC;Lin C;Hsieh CC;Yang YJ;Hueng DY
高级别胶质瘤的特点是预后差。为了改善临床结果，迫切需要生物标记物来区分高级别胶质瘤的癌靶点。端粒维持2(TELO2)调控细胞周期中的S期检查点，并参与DNA修复。然而，TELO2在高级别胶质瘤生存结局中的作用仍不清楚。本研究旨在探讨TELO2基因表达与高级别胶质瘤患者预后的关系。基于生物信息学研究，我们发现，Kaplan-Meier分析显示，与TELO2低表达的患者相比，TELO2高表达的患者存活时间更短(经对数等级检验，中位生存期59周比113周，p=0.0017，风险比：0.3505，95%CI：01824。-0.6735)。世界卫生组织IV级肿瘤组织中TELO2基因的表达显著高于非肿瘤对照组(p=2.85×10−9)。此外，WHO III级人脑胶质瘤的TELO2水平高于非肿瘤对照组(p=0.017)。通过定量RT-PCR、Western印迹和免疫组织化学(IHC)染色进一步验证组织芯片中TELO2基因的表达和蛋白水平。与正常脑对照组相比，人脑胶质瘤细胞中TELO2的mRNA和蛋白表达一直显著升高。此外，免疫组织化学染色显示，高级别胶质瘤的TELO2免疫染色分数高于低级别胶质瘤或正常脑对照。综上所述，人类高级别胶质瘤增加了TELO2 mRNA的表达，TELO2 mRNA的过度表达与较短的生存期相关，支持TELO2是人脑胶质瘤的肿瘤靶点。
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.
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影响因子：
158.5
作者：
Stupp, R;Mason, WP;Ryan, G
通讯作者：
Ryan, G
直到2001年，英格兰和威尔士的脑肿瘤生存。
影响因子：
8.8
作者：
Rachet, B.;Mitry, E.;Quinn, M. J.;Cooper, N.;Coleman, M. P.
通讯作者：
Coleman, M. P.
影响因子：
21.3
作者：
Collis, Spencer J.;Barber, Louise J.;Boulton, Simon J.
通讯作者：
Boulton, Simon J.
影响因子：
4.8
作者：
Jiang, N;Bénard, CY;Hekimi, S
通讯作者：
Hekimi, S
影响因子：
5.6
作者：
Hueng DY;Tsai WC;Chiou HY;Feng SW;Lin C;Li YF;Huang LC;Lin MH
通讯作者：
Lin MH