Differential correlation analysis of glioblastoma reveals immune ceRNA interactions predictive of patient survival.
Differential correlation analysis of glioblastoma reveals immune ceRNA interactions predictive of patient survival.
复制标题
胶质母细胞瘤的差异相关分析揭示了可预测患者生存的免疫 ceRNA 相互作用。
DOI：
10.1186/s12859-017-1557-4
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发表时间：
2017-02-28
影响因子：
3
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Chiu YC;Wang LJ;Lu TP;Hsiao TH;Chuang EY;Chen Y
最近的研究揭示了microRNA （miRNA）在竞争内源RNA （ceRNA）相互作用中的新作用：两个基因（ceRNA）可以通过竞争共同靶向miRNA来实现共表达。个体生物学研究表明，ceRNA相互作用在多形性胶质母细胞瘤（GBM）中具有重要的致癌/肿瘤抑制功能。然而，目前还没有系统的分析来探讨ceRNA相互作用的功能景观和预后意义。考虑到ceRNA相互作用是高度条件特异性的，并受mirna表达丰度的调节，我们通过差异相关分析设计了ceRNA推断，以确定mirna调节的ceRNA对。分析样本配对的miRNA和GBM的基因表达谱，我们的数据表明，这种基因相互作用的替代层在全球信息流中是必不可少的。功能注释分析显示其参与脑内激活过程，如突触传递，以及关键的肿瘤相关功能。值得注意的是，一项系统的生存分析表明，在三种免疫反应基因（CCL22、IL2RB和IRF4）中，ceRNA-ceRNA相互作用的强度，而不是单个cerna的表达丰度，可以预测患者的生存。预后价值在两个独立的队列中得到验证。这项工作解决了缺乏对ceRNA相互作用在GBM中的功能和预后相关性的全面探索。该方法有效可靠，在gbm相关功能及预后方面具有重要意义。ceRNA相互作用的突出作用为进一步的生物学和临床研究提供了基础。本文的在线版本（doi:10.1186/s12859-017-1557-4）包含补充材料，可供授权用户使用。
Recent studies illuminated a novel role of microRNA (miRNA) in the competing endogenous RNA (ceRNA) interaction: two genes (ceRNAs) can achieve coexpression by competing for a pool of common targeting miRNAs. Individual biological investigations implied ceRNA interaction performs crucial oncogenic/tumor suppressive functions in glioblastoma multiforme (GBM). Yet, a systematic analysis has not been conducted to explore the functional landscape and prognostic significance of ceRNA interaction. Incorporating the knowledge that ceRNA interaction is highly condition-specific and modulated by the expressional abundance of miRNAs, we devised a ceRNA inference by differential correlation analysis to identify the miRNA-modulated ceRNA pairs. Analyzing sample-paired miRNA and gene expression profiles of GBM, our data showed that this alternative layer of gene interaction is essential in global information flow. Functional annotation analysis revealed its involvement in activated processes in brain, such as synaptic transmission, as well as critical tumor-associated functions. Notably, a systematic survival analysis suggested the strength of ceRNA-ceRNA interactions, rather than expressional abundance of individual ceRNAs, among three immune response genes (CCL22, IL2RB, and IRF4) is predictive of patient survival. The prognostic value was validated in two independent cohorts. This work addresses the lack of a comprehensive exploration into the functional and prognostic relevance of ceRNA interaction in GBM. The proposed efficient and reliable method revealed its significance in GBM-related functions and prognosis. The highlighted roles of ceRNA interaction provide a basis for further biological and clinical investigations. The online version of this article (doi:10.1186/s12859-017-1557-4) contains supplementary material, which is available to authorized users.