Department of Applied Mathematics, University of Waterloo, Waterloo, Ontario, Canada.
PLoS One. 2013 May 29;8(5):e64169. doi: 10.1371/journal.pone.0064169. Print 2013.
In this manuscript, we use genetic data to provide a three-faceted analysis on the links between molecular subclasses of glioblastoma, epithelial-to-mesenchymal transition (EMT) and CD133 cell surface protein. The contribution of this paper is three-fold: First, we use a newly identified signature for epithelial-to-mesenchymal transition in human mammary epithelial cells, and demonstrate that genes in this signature have significant overlap with genes differentially expressed in all known GBM subtypes. However, the overlap between genes up regulated in the mesenchymal subtype of GBM and in the EMT signature was more significant than other GBM subtypes. Second, we provide evidence that there is a negative correlation between the genetic signature of EMT and that of CD133 cell surface protein, a putative marker for neural stem cells. Third, we study the correlation between GBM molecular subtypes and the genetic signature of CD133 cell surface protein. We demonstrate that the mesenchymal and neural subtypes of GBM have the strongest correlations with the CD133 genetic signature. While the mesenchymal subtype of GBM displays similarity with the signatures of both EMT and CD133, it also exhibits some differences with each of these signatures that are partly due to the fact that the signatures of EMT and CD133 are inversely related to each other. Taken together these data shed light on the role of the mesenchymal transition and neural stem cells, and their mutual interaction, in molecular subtypes of glioblastoma multiforme.
在本手稿中，我们使用遗传数据对胶质母细胞瘤的分子亚型、上皮-间充质转化（EMT）和 CD133 细胞表面蛋白之间的联系进行了三方面的分析。本文的贡献有三点：首先，我们使用新鉴定的人类乳腺上皮细胞上皮-间充质转化特征，证明该特征中的基因与所有已知 GBM 亚型中差异表达的基因有显著重叠。然而，GBM 间充质亚型中上调的基因与 EMT 特征中的基因重叠比其他 GBM 亚型更为显著。其次，我们提供证据表明 EMT 的遗传特征与 CD133 细胞表面蛋白的遗传特征呈负相关，CD133 细胞表面蛋白是神经干细胞的一个假定标志物。第三，我们研究了 GBM 分子亚型与 CD133 细胞表面蛋白遗传特征之间的相关性。我们证明 GBM 的间充质和神经亚型与 CD133 遗传特征的相关性最强。虽然 GBM 的间充质亚型与 EMT 和 CD133 特征都具有相似性，但它与这两个特征也存在一些差异，部分原因是 EMT 和 CD133 特征彼此呈负相关。总之，这些数据阐明了间充质转化和神经干细胞及其相互作用在多形性胶质母细胞瘤分子亚型中的作用。
