Quantitatively determined survivin expression levels are of prognostic value in human gliomas
Quantitatively determined survivin expression levels are of prognostic value in human gliomas
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DOI：
10.1200/jco.20.4.1063
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发表时间：
2002-02-15
影响因子：
45.3
通讯作者：
Loeffler, JS
中科院分区：
文献类型：
--
作者：
Chakravarti, A;Noll, E;Loeffler, JS
目的：Survivin是新近克隆和鉴定的一种新的抗细胞凋亡基因。它的表达已经被发现在几种肿瘤类型中具有预后意义。这是首次研究Survivin在人脑胶质瘤中的表达对预后的意义。材料和方法：我们用定量Western印迹结合密度计量学方法检测了92例有冰冻组织可供分析的胶质瘤组织中Survivin蛋白的表达水平。Survivin的阳性和表达水平与肿瘤的组织病理学特征、细胞凋亡率(以caspase 3的裂解或激活水平来衡量)和临床转归相关。当考虑到所有胶质瘤患者时，可检测到Survivin表达的患者与未检测到Survivin表达的患者相比，总体生存时间显著缩短(P<；.0001)。尽管多形性胶质母细胞瘤(GBM)患者的Survivin阳性率和Survivin表达水平显著高于非GBM患者(P<；0.0001)，但Survivin表达的预后价值似乎独立于组织学。Survivin阳性的GBM患者的总体生存时间显著短于Survivin阴性的GBM患者(P<；.0001)。同样，Survivin阳性的非GBM患者的生存时间比Survivin阴性的非GBM患者短(P=.029)。此外，当考虑到所有胶质瘤患者时，Survivin表达水平的增加与生存时间的减少显著相关，对GBM患者也是如此(P<；.0001)。结论：定量检测Survivin的阳性表达和蛋白表达水平对人脑胶质瘤的预后有重要意义，并可能与肿瘤的凋亡能力降低有关。(C)2002年，由美国临床肿瘤学会提供。
Purpose: Survivin is a novel antiapoptotic gene that has been recently cloned and characterized. Its expression has been found to be of prognostic significance in several tumor types. This is the first study on the prognostic significance of survivin expression in human gliomas.Materials and Methods: We used quantitative Western blot analysis with densitometry to determine survivin protein expression levels in 92 glioma cases for which frozen tissue was available for analysis. Survivin positivity and expression levels were correlated with histopothologic features of the tumors, apoptosis (as measured by cleaved, or activated, caspase 3 levels), and clinical outcome.Results: Survivin expression has clear prognostic value in human gliomas. Patients with detectable survivin expression had significantly shorter overall survival times (P < .0001) compared with those without detectable expression when all glioma patients were considered. Although glioblastoma multiforme (GBM) patients had significantly higher rates of survivin positivity and higher levels of survivin expression (P < .0001) than their non-GBM counterparts, the prognostic value of survivin expression seemed to be independent of histology alone. Survivin-positive GBM patients had significantly shorter overall survival times compared with survivin-negative GBM patients (P < .0001). Likewise, survivin-positive non-GBM patients had shorter survival times compared with survivin-negative non-GBM patients (P = .029). Furthermore, increasing levels of survivin expression significantly correlated with reduced survival times when all glioma patients were considered, and markedly so for GBM patients (P < .0001). Increasing survivin levels significantly correlated with reduced expression of cleaved caspase 3, indicating its association with antiapoptotic activity.Conclusion: Survivin positivity and protein expression levels, as determined quantitatively, are of significant prognostic value in human gliomas and seem to be associated with reduced apoptotic capacity of these tumors. (C) 2002 by American Society of Clinical Oncology.