The expression of PAX6, PTEN, vascular endothelial growth factor, and epidermal growth factor receptor in gliomas: relationship to tumor grade and survival.
The expression of PAX6, PTEN, vascular endothelial growth factor, and epidermal growth factor receptor in gliomas: relationship to tumor grade and survival.
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发表时间：
2003-08
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通讯作者：
Yi-Hong Zhou;Fang Tan;K. Hess;W. Yung
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作者：
Yi-Hong Zhou;Fang Tan;K. Hess;W. Yung
恶性星形细胞胶质瘤，包括间变性星形细胞瘤（AA）和多形性胶质母细胞瘤（GBM），是由多种基因干扰和基因表达失调引起的。识别遗传预后标志物可能比单独的大体病理学更有助于对胶质瘤患者进行分层。实验设计使用来自86名患者的胶质瘤和邻近正常组织的mRNA通过逆转录酶产生cDNA。用于分析的组织包括45个AA、42个GBM和7个邻近正常组织样本。PAX 6、PTEN、血管内皮生长因子（VEGF）和表皮生长因子受体（EGFR）基因表达的水平使用实时定量逆转录-PCR进行定量，并标准化为β-肌动蛋白。使用的所有统计检验均为双侧检验。结果PAX 6在GBM中的表达明显低于AA（P < 0.0001）。PTEN、EGFR和VEGF表达的相对水平在胶质瘤分级之间也有显著差异。对胶质瘤样本进行多变量考克斯分析，调整患者年龄、组织学、复发状态和PTEN、EGFR、VEGF和PAX 6水平（7个变量），显示恶性星形细胞胶质瘤中PAX 6低水平表达与患者不良结局之间存在相关性（风险比，0.34; 95%置信区间，0.18-0.63）。递归分割分析显示，与一个或两个基因的低表达值相比，PTEN和PAX 6高表达值的患者的预后良好（P < 0.0001）。结论PAX 6、PTEN和VEGF的表达水平是独立的预后指标，而EGFR的表达水平不是独立的预后指标，包含7个变量的模型能够解释恶性星形细胞胶质瘤患者生存时间的55%的变异。
PURPOSE Malignant astrocytic gliomas, including anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM), result from various genetic perturbations and dysregulated gene expression. Identifying genetic prognostic markers could be more useful for stratifying glioma patients than gross pathology alone. EXPERIMENTAL DESIGN cDNAs were generated by reverse transcriptase using mRNAs from gliomas and adjacent normal tissues from 86 patients. The tissues used for analysis were 45 AAs, 42 GBMs, and 7 samples of adjacent normal tissue. The levels of PAX6, PTEN, vascular endothelial growth factor (VEGF), and epidermal growth factor receptor (EGFR) gene expression were quantified using real-time quantitative reverse transcription-PCR and normalized to beta-actin. All statistical tests used were two-sided. RESULTS PAX6 expression was significantly reduced in GBM compared with AA (P < 0.0001). The relative levels of PTEN, EGFR, and VEGF expression also differed significantly among glioma grades. Multivariate Cox analysis of glioma samples, adjusting for patient age, histology, recurrent status, and levels of PTEN, EGFR, VEGF, and PAX6 (7 variables) showed a correlation between a low level of PAX6 expression in malignant astrocytic gliomas and unfavorable patient outcomes (hazard ratio, 0.34; 95% confidence interval, 0.18-0.63). Recursive partitioning analysis showed a favorable outcome for patients with high expression values of PTEN and PAX6 compared with low expression values of one or both genes (P < 0.0001). CONCLUSION The expression levels of PAX6, PTEN, and VEGF but not EGFR were independent prognostic markers, and the model including 7 variables was able to account for 55% of the variation in survival times for malignant astrocytic glioma patients.