AP001056.1, A Prognosis-Related Enhancer RNA in Squamous Cell Carcinoma of the Head and Neck
AP001056.1, A Prognosis-Related Enhancer RNA in Squamous Cell Carcinoma of the Head and Neck
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DOI：
10.3390/cancers11030347
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发表时间：
2019-03-01
期刊：
影响因子：
5.2
通讯作者：
Nylander, Karin
中科院分区：
文献类型：
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作者：
Gu, Xiaolian;Wang, Lixiao;Nylander, Karin
越来越多的长链非编码RNA（lncRNA）与头颈部鳞状细胞癌（SCCHN）有关。lncRNA的一个亚类，称为增强子RNA（eRNA），来源于增强子区域并且可以有助于增强子功能。在这项研究中，我们开发了一个综合的数据分析方法，以确定关键eRNA在SCCHN。组织特异性增强子衍生的RNA及其先前使用计算管道PreSTIGE预测的调控基因被认为是推定的eRNA靶对。交互式网络服务器TANRIC（癌症非编码RNA图谱）和cBioPortal用于探索癌症基因组图谱（TCGA）项目的RNA水平和临床数据。要求关键eRNA应显示与总生存率（Kaplan-Meier对数秩检验，p < 0.05）和预测靶点（相关系数r > 0.4，p < 0.001）的显著相关性，我们鉴定了五种关键eRNA候选物。最显著的存活相关eRNA是AP001056.1，其ICOSLG编码免疫检查点蛋白作为其调节靶标。另外1640个基因也与AP001056.1显着相关（r > 0.4，p < 0.001），其中“免疫系统过程”是最显着富集的生物过程（调整后p < 0.001）。我们的研究结果表明，AP001056.1是SCCHN中关键的免疫相关eRNA，对临床结果有积极影响。
A growing number of long non-coding RNAs (lncRNAs) have been linked to squamous cell carcinoma of the head and neck (SCCHN). A subclass of lncRNAs, termed enhancer RNAs (eRNAs), are derived from enhancer regions and could contribute to enhancer function. In this study, we developed an integrated data analysis approach to identify key eRNAs in SCCHN. Tissue-specific enhancer-derived RNAs and their regulated genes previously predicted using the computational pipeline PreSTIGE, were considered as putative eRNA-target pairs. The interactive web servers, TANRIC (the Atlas of Noncoding RNAs in Cancer) and cBioPortal, were used to explore the RNA levels and clinical data from the Cancer Genome Atlas (TCGA) project. Requiring that key eRNAs should show significant associations with overall survival (Kaplan-Meier log-rank test, p < 0.05) and the predicted target (correlation coefficient r > 0.4, p < 0.001), we identified five key eRNA candidates. The most significant survival-associated eRNA was AP001056.1 with ICOSLG encoding an immune checkpoint protein as its regulated target. Another 1640 genes also showed significant correlation with AP001056.1 (r > 0.4, p < 0.001), with the "immune system process" being the most significantly enriched biological process (adjusted p < 0.001). Our results suggest that AP001056.1 is a key immune-related eRNA in SCCHN with a positive impact on clinical outcome.