Dynamic TF-lncRNA Regulatory Networks Revealed Prognostic Signatures in the Development of Ovarian Cancer
Dynamic TF-lncRNA Regulatory Networks Revealed Prognostic Signatures in the Development of Ovarian Cancer
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动态 TF-lncRNA 调控网络揭示了卵巢癌发展中的预后特征
DOI：
10.3389/fbioe.2020.00460
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发表时间：
2020-05-13
影响因子：
5.7
通讯作者：
Wang, Peng
中科院分区：
文献类型：
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作者：
Guo, Qiuyan;Wang, Junwei;Wang, Peng
卵巢癌（OC）的病理发展是一个复杂的过程，取决于编码和非编码基因的多重改变。因此，重要的是捕捉OC发展过程中的转录调控事件，并确定可靠的标记物，用于预测患者的临床结局。分析了来自癌症基因组图谱（TCGA）的399例不同阶段的卵巢浆液性囊腺癌患者的数据集。通过整合高通量RNA分子谱和转录因子结合信息，构建了阶段特异性转录因子（TF）长的非编码RNA（lncRNA）调控网络。进行系统分析以表征OC不同阶段的TF-lncRNA调节行为。采用考克斯回归分析和Kaplan-Meier生存曲线评价TF-lncRNA调节和小集团的预后效率。阶段特异性TF-lncRNA调控网络在三个OC阶段（II，III和IV）表现出共同的结构和特定的拓扑结构的风险TF和lncRNA。不同阶段的TF-lncRNA活性曲线显示TF在调节lncRNA方面具有高度的阶段选择性。功能分析表明，TF-lncRNA相互作用组参与特定的病理过程中的OC的发展。在STAT 3-FOS共调节组中，TF STAT 3和FOS在不同OC阶段选择性地调节靶lncRNA。进一步的生存分析表明，这种TF-lncRNA biclique可能具有预测OC预后的潜力。本研究揭示了TF-lncRNA调控网络的拓扑学和动力学原理，为进一步分析OC的阶段特异性调控机制提供了依据。
The pathological development of ovarian cancer (OC) is a complex progression that depends on multiple alterations of coding and non-coding genes. Therefore, it is important to capture the transcriptional-regulating events during the progression of OC development and to identify reliable markers for predicting clinical outcomes in patients. A dataset of 399 ovarian serous cystadenocarcinoma patients at different stages from The Cancer Genome Atlas (TCGA) was analyzed. Stage-specific transcription factor (TF)-long non-coding RNA (lncRNA) regulatory networks were constructed by integrating high-throughput RNA molecular profiles and TF binding information. Systematic analysis was performed to characterize the TF-lncRNA-regulating behaviors across different stages of OC. Cox regression analysis and Kaplan-Meier survival curves were used to evaluate the prognostic efficiency of TF-lncRNA regulations and cliques. The stage-specific TF-lncRNA regulatory networks at three OC stages (II, III, and IV) exhibited common structures and specific topologies of risk TFs and lncRNAs. A TF-lncRNA activity profile across different stages revealed that TFs were highly stage-selective in regulating lncRNAs. Functional analysis indicated that groups of TF-lncRNA interactions were involved in specific pathological processes in the development of OC. In a STAT3-FOS co-regulating clique, the TFs STAT3 and FOS were selectively regulating target lncRNAs across different OC stages. Further survival analysis indicated that this TF-lncRNA biclique may have the potential for predicting OC prognosis. This study revealed the topological and dynamic principles of TF-lncRNA regulatory networks and provided a resource for further analysis of stage-specific regulating mechanisms of OC.