Merck KGaA, Merck Serono - Discovery Bioinformatics, Darmstadt, Germany.
Transl Oncol. 2012 Aug;5(4):297-304. doi: 10.1593/tlo.12214. Epub 2012 Aug 1.
Recent evidence suggests that cytomegalovirus infection contributes to the development of medulloblastomas. Differential activation of antiviral expression programs in medulloblastomas has not been investigated yet. In this study, we assess the relevance of an antiviral transcriptional response in medulloblastomas. We analyzed a gene expression signature of type I interferon response in three public gene expression data sets of medulloblastomas. Interferon response genes were found to be significantly coordinately regulated in two independent studies. We distilled a signature of 10 interferon response genes from two data sets. This signature exhibited strongly significant gene-versus-gene correlation of expression levels across samples in a third external medulloblastoma data set. Our medulloblastoma IFN signature identified a previously unrecognized patient subgroup partially overlapping the WNT and SHH subtypes proposed by others. We conclude that significant traces of differential activation of antiviral transcriptional response can be found in three independent medulloblastoma patient cohorts. This IFN activation signal often coincides with reduced proliferation scores. Our proposed 10-gene type I IFN response gene signature could help to assess antiviral states in further gene expression data sets of medulloblastomas or other cancers.
最近的证据表明，巨细胞病毒感染有助于成神经管细胞瘤的发展。然而，抗病毒表达程序在成神经管细胞瘤中的差异激活尚未得到研究。在这项研究中，我们评估了成神经管细胞瘤中抗病毒转录反应的相关性。我们分析了三个成神经管细胞瘤公共基因表达数据集的 I 型干扰素反应的基因表达特征。干扰素反应基因在两项独立研究中被发现具有显著的协调调节。我们从两个数据集提炼出了 10 个干扰素反应基因的特征。该特征在第三个外部成神经管细胞瘤数据集的样本中表现出强烈的显著基因对基因表达水平的相关性。我们的成神经管细胞瘤 IFN 特征确定了一个以前未被识别的患者亚组，该亚组部分与其他人提出的 WNT 和 SHH 亚型重叠。我们得出结论，在三个独立的成神经管细胞瘤患者队列中可以发现抗病毒转录反应的显著差异激活痕迹。这种 IFN 激活信号通常与增殖评分降低相关。我们提出的 10 个基因 I 型干扰素反应基因特征可用于评估成神经管细胞瘤或其他癌症的进一步基因表达数据集中的抗病毒状态。
