He Qun, Tian Linli, Jiang Hao, Zhang Jiarui, Li Qiang, Sun Yanan, Zhao Jiannan, Li Huijun, Liu Ming
Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital, Harbin Medical University, Harbin, China.
Department of Otolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, China.
Oncotarget. 2017 Feb 7;8(6):9525-9534. doi: 10.18632/oncotarget.13627.
Competitive endogenous RNAs (ceRNAs) act as molecular sponges for microRNAs (miRNAs), and are associated with tumorigenesis in various cancers, including laryngeal cancer (LC). In this work, we constructed an LC-specific inflammatory gene-related ceRNA network (IceNet). In IceNet, ceRNAs targeting inflammation-related genes tended to be network hubs. Additionally, the betweenness centralities of these hub ceRNAs were higher than those of the inflammation-related genes themselves, indicating that the hub ceRNAs in this study played critical roles in communication between IceNet molecules. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses indicated that IceNet molecules are associated with multiple cancer-related functions and signaling pathways. Using cFinder software and survival analyses, we identified a potential prognostic module within IceNet that contains 18 mRNAs and a long non-coding RNA (lncRNA), and we effectively stratified patients into high- and low-risk subgroups with different survival outcomes, independent of patient age and tumor grade. This 18-mRNA and one-lncRNA module provides a novel mechanism for potentially improving LC patient prognostic predictions. Applying the module clinically to differentiate high- and low-risk patients could inform therapeutic decision making and ultimately improve patient outcomes. In addition, these results demonstrate the potential importance of IceNet hub ceRNAs in LC development and progression.
竞争性内源RNA(ceRNA)作为微小RNA(miRNA)的分子海绵,与包括喉癌(LC)在内的多种癌症的肿瘤发生相关。在本研究中,我们构建了一个喉癌特异性炎症基因相关ceRNA网络(IceNet)。在IceNet中,靶向炎症相关基因的ceRNA倾向于成为网络枢纽。此外,这些枢纽ceRNA的中介中心性高于炎症相关基因本身,表明本研究中的枢纽ceRNA在IceNet分子间的通讯中发挥关键作用。基因本体论和京都基因与基因组百科全书通路分析表明,IceNet分子与多种癌症相关功能和信号通路有关。使用cFinder软件和生存分析,我们在IceNet中鉴定出一个潜在的预后模块,该模块包含18个mRNA和一个长链非编码RNA(lncRNA),并且我们有效地将患者分为具有不同生存结果的高风险和低风险亚组,与患者年龄和肿瘤分级无关。这个由18个mRNA和1个lncRNA组成的模块为潜在改善喉癌患者预后预测提供了一种新机制。临床上应用该模块区分高风险和低风险患者可以为治疗决策提供依据,并最终改善患者预后。此外,这些结果证明了IceNet枢纽ceRNA在喉癌发生发展中的潜在重要性。