Immunohistochemical analysis-based proteomic subclassification of newly diagnosed glioblastomas
Immunohistochemical analysis-based proteomic subclassification of newly diagnosed glioblastomas
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DOI：
10.1111/j.1349-7006.2012.02377.x
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发表时间：
2012-10-01
期刊：
影响因子：
5.7
通讯作者：
Wakabayashi, Toshihiko
中科院分区：
文献类型：
--
作者：
Motomura, Kazuya;Natsume, Atsushi;Wakabayashi, Toshihiko
癌症基因组图谱 (TCGA) 研究网络最近对多形性胶质母细胞瘤 (GBM) 进行的基因表达和拷贝数分析表明，该肿瘤存在不同的亚型。然而，这些方法可能不容易应用于常规临床实践。在当前的研究中，我们的目标是通过整合 GBM 的基因组和表观基因组图谱，建立基于蛋白质组学的 GBM 亚分类。我们根据综合免疫组织化学观察确定的表达模式，结合 DNA 拷贝数和 DNA 甲基化模式，对 79 例新诊断的 GBM 进行了细分。我们分类的临床相关性在 TCGA 数据集中得到了独立验证。共识聚类确定了四种不同的 GBM 亚型：少突胶质细胞前体 (OPC) 型、分化少突胶质细胞 (DOC) 型、星形细胞间充质 (AsMes) 型和混合型。 OPC 类型的特点是 Olig2、PDGFRA、p16、p53 和突触素得分高度阳性。相比之下，AsMes 类型与巢蛋白、CD44 和足足蛋白的强烈表达密切相关，并具有高胶质纤维酸性蛋白评分。 OPC 型患者的中位总生存期显着长于 AsMes 型患者（19.9 个月 vs 12.8 个月）。这一发现与 Oncomine 对 TCGA 数据集的分析一致，该分析表明 PDGFRA 和 Olig2 是有利的预后因素，而 podoplanin 和 CD44 与不良的临床结果相关。这是第一项基于免疫组织化学分析建立 GBM 亚分类的研究。我们的研究将揭示在日常神经病理学实践中可能可行的个性化疗法。 （癌症科学，doi：10.1111/j.1349-7006.2012.02377.x，2012）
Recent gene expression and copy number profilings of glioblastoma multiforme (GBM) by The Cancer Genome Atlas (TCGA) Research Network suggest the existence of distinct subtypes of this tumor. However, these approaches might not be easily applicable in routine clinical practice. In the current study, we aimed to establish a proteomics-based subclassification of GBM by integrating their genomic and epigenomic profiles. We subclassified 79 newly diagnosed GBM based on expression patterns determined by comprehensive immunohistochemical observation in combination with their DNA copy number and DNA methylation patterns. The clinical relevance of our classification was independently validated in TCGA datasets. Consensus clustering identified the four distinct GBM subtypes: Oligodendrocyte Precursor (OPC) type, Differentiated Oligodendrocyte (DOC) type, Astrocytic Mesenchymal (AsMes) type and Mixed type. The OPC type was characterized by highly positive scores of Olig2, PDGFRA, p16, p53 and synaptophysin. In contrast, the AsMes type was strongly associated with strong expressions of nestin, CD44 and podoplanin, with a high glial fibrillary acidic protein score. The median overall survival of OPC-type patients was significantly longer than that of the AsMes-type patients (19.9 vs 12.8 similar to months). This finding was in agreement with the Oncomine analysis of TCGA datasets, which revealed that PDGFRA and Olig2 were favorable prognostic factors and podoplanin and CD44 were associated with a poor clinical outcome. This is the first study to establish a subclassification of GBM on the basis of immunohistochemical analysis. Our study will shed light on personalized therapies that might be feasible in daily neuropathological practice. (Cancer Sci, doi: 10.1111/j.1349-7006.2012.02377.x, 2012)