A gene expression signature for NOTCH receptor activation. A gene expression signature for NOTCH receptor activation

In many solid cancers and leukemia’s deregulation of the NOTCH signalling pathway is frequently observed, which led to the initiation of clinical trials. However, results from clinical trials using small molecule inhibitors of NOTCH so far are disappointing due to low efficacy and a high toxicity. One shortcoming in these patient studies is the lack of prognostic, predictive and pharmacological biomarkers that could accompany trial design and treatment adaptation. The purpose of this study was to develop an mRNA based NOTCH isoform-specific gene expression signature, which allows for robust identification of NOTCH activity in human tumours. Overall design: Here we generated gene expression profile of 15 cell lines using RNA-Sequening. In total, we have 5 groups. We have control group (EV) and 4 gorups each expressing different NOTCH receptor. So, NOTCH 1-4 groups. In total, we have 15 RNA-Seq datasets (5 groups and 3 replicate per group= 15 samples)

在多种实体瘤与白血病中，NOTCH信号通路（NOTCH signalling pathway）的失调现象频繁出现，这推动了相关临床试验的开展。然而迄今为止，使用NOTCH小分子抑制剂（small molecule inhibitors）开展的临床试验结果均不尽如人意，究其原因在于疗效低下且毒性较强。此类患者研究的一大短板在于缺乏可辅助临床试验设计与治疗方案调整的预后、预测及药理学生物标志物。本研究旨在构建基于mRNA的NOTCH亚型特异性基因表达特征，以实现在人类肿瘤样本中精准识别NOTCH通路活性。整体实验设计：本研究通过RNA测序（RNA-Seq）技术构建了15株细胞系的基因表达谱。实验共分为5组，分别为空载对照（EV，empty vector）组，以及分别表达不同NOTCH受体的4组样本，即NOTCH 1~4组。总计包含15份RNA测序数据集（5组，每组设置3次生物学重复，合计15个样本）