Lee Yohan, Scheck Adrienne C, Cloughesy Timothy F, Lai Albert, Dong Jun, Farooqi Haumith K, Liau Linda M, Horvath Steve, Mischel Paul S, Nelson Stanley F
Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095-7088 USA.
BMC Med Genomics. 2008 Oct 21;1:52. doi: 10.1186/1755-8794-1-52.
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.
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.
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.
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.
胶质母细胞瘤是成人中最常见的原发性脑肿瘤。尽管患者预后较差，但基因表达谱分析已检测到一些特征，可根据组织病理学和临床变量对胶质母细胞瘤进行亚分类。一种由基因表达特征定义的胶质母细胞瘤类别被称为神经前体细胞型（PN），与其他基于基因表达的胶质母细胞瘤亚型相比，患者生存期显著更长。发病年龄是患者生存时长的主要预测因素，年轻患者比老年患者生存时间更长。这种生存优势的原因尚不清楚。
我们收集了267个胶质母细胞瘤CEL文件，并相对于同一Affymetrix平台的其他微阵列对其进行标准化处理。U133A和U133 Plus 2.0阵列上的377个探针集用于基因投票策略，同时结合旧版U95Av2阵列上177个匹配基因的探针集。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。
除新数据外，对已发表数据的这项荟萃分析证实了四种不同的胶质母细胞瘤表达特征的存在。此外，正如预期的那样，PN亚型胶质母细胞瘤患者生存期更长。然而，在控制PN亚型后，患者诊断时的年龄并不能预测生存时间。
当按基因表达组对患者进行分层时，年轻患者的生存优势消失。因此，胶质母细胞瘤中年龄效应的主要原因是年轻患者中PN胶质母细胞瘤的发生率相对于老年患者更高。
