Gu Xiaolian, Wang Lixiao, Boldrup Linda, Coates Philip J, Fahraeus Robin, Sgaramella Nicola, Wilms Torben, Nylander Karin
Department of Medical Biosciences/Pathology, Umeå University, 90185 Umeå, Sweden.
RECAMO, Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic.
Cancers (Basel). 2019 Mar 11;11(3):347. doi: 10.3390/cancers11030347.
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, < 0.05) and the predicted target (correlation coefficient > 0.4, < 0.001), we identified five key eRNA candidates. The most significant survival-associated eRNA was with encoding an immune checkpoint protein as its regulated target. Another 1640 genes also showed significant correlation with ( > 0.4, < 0.001), with the "immune system process" being the most significantly enriched biological process (adjusted < 0.001). Our results suggest that is a key immune-related eRNA in SCCHN with a positive impact on clinical outcome.
越来越多的长链非编码RNA（lncRNA）与头颈部鳞状细胞癌（SCCHN）相关联。lncRNA的一个亚类，称为增强子RNA（eRNA），源自增强子区域，并可能有助于增强子功能。在本研究中，我们开发了一种综合数据分析方法来鉴定SCCHN中的关键eRNA。先前使用计算管道PreSTIGE预测的组织特异性增强子衍生RNA及其调控基因被视为假定的eRNA-靶标对。交互式网络服务器TANRIC（癌症非编码RNA图谱）和cBioPortal用于探索来自癌症基因组图谱（TCGA）项目的RNA水平和临床数据。要求关键eRNA应与总生存期（Kaplan-Meier对数秩检验，<0.05）和预测靶标（相关系数>0.4，<0.001）显示出显著关联，我们鉴定出五个关键eRNA候选物。与生存最显著相关的eRNA是，其编码一种免疫检查点蛋白作为其调控靶标。另外1640个基因也与显示出显著相关性（>0.4，<0.001），其中“免疫系统过程”是最显著富集的生物学过程（校正后<0.001）。我们的结果表明，是SCCHN中一种关键的免疫相关eRNA，对临床结局有积极影响。
