Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, 77030, USA.
Acta Neuropathol. 2012 May;123(5):727-38. doi: 10.1007/s00401-012-0941-4. Epub 2012 Feb 10.
Patients with ependymoma exhibit a wide range of clinical outcomes that are currently unexplained by clinical or histological factors. Little is known regarding molecular biomarkers that could predict clinical behavior. Since recent data suggest that these tumors display biological characteristics according to their location (cerebral vs. infratentorial vs. spinal cord), rather than explore a broad spectrum of ependymoma, we focused on molecular alterations in ependymomas arising in the infratentorial compartment. Unsupervised clustering of available gene expression microarray data revealed two major subgroups of infratentorial ependymoma. Group 1 tumors over expressed genes that were associated with mesenchyme, Group 2 tumors showed no distinct gene ontologies. To assess the prognostic significance of these gene expression subgroups, real-time reverse transcriptase polymerase chain reaction assays were performed on genes defining the subgroups in a training set. This resulted in a 10-gene prognostic signature. Multivariate analysis showed that the 10-gene signature was an independent predictor of recurrence-free survival after adjusting for clinical factors. Evaluation of an external dataset describing subgroups of infratentorial ependymomas showed concordance of subgroup definition, including validation of the mesenchymal subclass. Importantly, the 10-gene signature was validated as a predictor of recurrence-free survival in this dataset. Taken together, the results indicate a link between clinical outcome and biologically identified subsets of infratentorial ependymoma and offer the potential for prognostic testing to estimate clinical aggressiveness in these tumors.
患者的室管膜瘤表现出广泛的临床结果，目前无法用临床或组织学因素来解释。对于可以预测临床行为的分子生物标志物知之甚少。由于最近的数据表明，这些肿瘤根据其位置（大脑与小脑或脊髓）显示出不同的生物学特征，而不是广泛探索室管膜瘤，我们专注于发生在小脑的室管膜瘤的分子改变。对现有基因表达微阵列数据进行无监督聚类，揭示了小脑室管膜瘤的两个主要亚群。第 1 组肿瘤过度表达与间质相关的基因，第 2 组肿瘤没有明显的基因本体论。为了评估这些基因表达亚组的预后意义，在训练集中对定义亚组的基因进行了实时逆转录聚合酶链反应检测。这产生了 10 个基因的预后标志。多变量分析表明，在调整临床因素后，10 个基因标志是无复发生存的独立预测因子。对描述小脑室管膜瘤亚组的外部数据集的评估显示，亚组定义的一致性，包括对间充质亚组的验证。重要的是，在这个数据集验证了 10 个基因标志是无复发生存的预测因子。综上所述，这些结果表明临床结果与小脑室管膜瘤生物学鉴定的亚组之间存在联系，并为这些肿瘤的临床侵袭性估计提供了预后检测的潜力。
