文章：

胶质瘤细胞中假定间充质刺激因子的转录组学特征差异

Divergent transcriptomic signatures from putative mesenchymal stimuli in glioblastoma cells 

原文发布日期：2024-02-09 

英文摘要：

In glioblastoma, a mesenchymal phenotype is associated with especially poor patient outcomes. Various glioblastoma microenvironmental factors and therapeutic interventions are purported drivers of the mesenchymal transition, but the degree to which these cues promote the same mesenchymal transitions and the uniformity of those transitions, as defined by molecular subtyping systems, is unknown. Here, we investigate this question by analyzing publicly available patient data, surveying commonly measured transcripts for mesenchymal transitions in glioma-initiating cells (GIC), and performing next-generation RNA sequencing of GICs. Analysis of patient tumor data reveals that TGFβ, TNFα, and hypoxia signaling correlate with the mesenchymal subtype more than the proneural subtype. In cultured GICs, the microenvironment-relevant growth factors TGFβ and TNFα and the chemotherapeutic temozolomide promote expression of commonly measured mesenchymal transcripts. However, next-generation RNA sequencing reveals that growth factors and temozolomide broadly promote expression of both mesenchymal and proneural transcripts, in some cases with equal frequency. These results suggest that glioblastoma mesenchymal transitions do not occur as distinctly as in epithelial-derived cancers, at least as determined using common subtyping ontologies and measuring response to growth factors or chemotherapeutics. Further understanding of these issues may identify improved methods for pharmacologically targeting the mesenchymal phenotype in glioblastoma. 

摘要翻译： 

在胶质母细胞瘤中，间充质表型与患者极差的预后密切相关。多种肿瘤微环境因素和治疗干预措施被认为是间质转化的驱动因素，但这些因素在多大程度上促进相同的间质转化过程，以及根据分子分型系统定义的转化一致性仍不明确。本研究通过分析公开的患者数据、检测胶质瘤起始细胞（GIC）中常用的间质转化转录标志物，并对GIC进行新一代RNA测序来探讨这一问题。对患者肿瘤数据的分析显示，TGFβ、TNFα和缺氧信号通路与间充质亚型的相关性高于前神经亚型。在培养的GIC中，与微环境相关的生长因子TGFβ和TNFα以及化疗药物替莫唑胺可促进常见间质转录标志物的表达。然而，新一代RNA测序显示生长因子和替莫唑胺广泛促进间充质和前神经转录标志物的表达，在某些情况下两者表达频率相当。这些结果表明，胶质母细胞瘤的间质转化并不像上皮源性癌症那样具有明显界限，至少通过常用分型标准及对生长因子或化疗药物的反应评估时如此。对这些问题的进一步理解可能为药物靶向胶质母细胞瘤间充质表型提供改进策略。

原文链接：

Divergent transcriptomic signatures from putative mesenchymal stimuli in glioblastoma cells