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首页> 外文期刊>BMC Medical Genomics >Gene expression analysis of glioblastomas identifies the major molecular basis for the prognostic benefit of younger age
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Gene expression analysis of glioblastomas identifies the major molecular basis for the prognostic benefit of younger age

机译：胶质母细胞瘤的基因表达分析确定了年轻年龄的预后益处的主要分子基础

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Background Glioblastomas are the most common primary brain tumour in adults. While the prognosis for patients is poor, gene expression profiling has detected signatures that can sub-classify GBMs relative to histopathology and clinical variables. One category of GBM defined by a gene expression signature is termed ProNeural (PN), and has substantially longer patient survival relative to other gene expression-based subtypes of GBMs. Age of onset is a major predictor of the length of patient survival where younger patients survive longer than older patients. The reason for this survival advantage has not been clear. Methods We collected 267 GBM CEL files and normalized them relative to other microarrays of the same Affymetrix platform. 377 probesets on U133A and U133 Plus 2.0 arrays were used in a gene voting strategy with 177 probesets of matching genes on older U95Av2 arrays. Kaplan-Meier curves and Cox proportional hazard analyses were applied in distinguishing survival differences between expression subtypes and age. Results This meta-analysis of published data in addition to new data confirms the existence of four distinct GBM expression-signatures. Further, patients with PN subtype GBMs had longer survival, as expected. However, the age of the patient at diagnosis is not predictive of survival time when controlled for the PN subtype. Conclusion The survival benefit of younger age is nullified when patients are stratified by gene expression group. Thus, the main cause of the age effect in GBMs is the more frequent occurrence of PN GBMs in younger patients relative to older patients.
机译：背景胶质母细胞瘤是成人中最常见的原发性脑肿瘤。尽管患者的预后较差，但基因表达谱检测已发现可以将GBM相对于组织病理学和临床变量进行亚分类的特征。由基因表达签名定义的一类GBM被称为ProNeural（PN），相对于其他基于基因表达的GBM亚型，其患者生存期更长。发病年龄是患者生存时间的主要预测指标，年轻患者的生存时间比老年患者更长。这种生存优势的原因尚不清楚。方法我们收集了267个GBM CEL文件，并相对于同一Affymetrix平台的其他微阵列将其标准化。在基因投票策略中，将U133A和U133 Plus 2.0阵列上的377个探针组与较旧的U95Av2阵列上的177个匹配基因的探针组用于基因投票策略。应用Kaplan-Meier曲线和Cox比例风险分析来区分表达亚型和年龄之间的生存差异。结果除新数据外，对已发布数据进行的荟萃分析还证实了存在四个不同的GBM表达签名。此外，PN亚型GBMs患者的生存期更长，正如预期的那样。但是，当控制PN亚型时，诊断时患者的年龄不能预测生存时间。结论按基因表达组对患者进行分层，无效了年轻患者的生存利益。因此，GBM中年龄效应的主要原因是相对于老年患者，年轻患者中PN GBM的发生更为频繁。

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