Identification of 4-lncRNA prognostic signature in head and neck squamous cell carcinoma
Identification of 4-lncRNA prognostic signature in head and neck squamous cell carcinoma
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DOI：
10.1002/jcb.28284
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发表时间：
2019-06-01
影响因子：
4
通讯作者：
Cheng, Jie
中科院分区：
文献类型：
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作者：
Diao, Pengfei;Song, Yue;Cheng, Jie
去调控的长链非编码RNA（lncRNA）与肿瘤发生密切相关，并可作为新的诊断和预后生物标志物。在这里，我们试图开发一种头颈部鳞状细胞癌（HNSCC）患者的预后lncRNA标签。从癌症基因组图谱数据库中检索499个HNSCC样本的原始RNA-seq数据，将其随机分为训练集和测试集。应用单变量考克斯回归生存分析、稳健的基于似然的生存模型和随机抽样迭代来鉴定训练队列中的预后lncRNA候选物。基于四种单独lncRNA的考克斯系数开发预后风险评分，如下插补：（0.14546 x RP 11 - 366 H4.1的表达水平）+（0.27106 x LINC 01123的表达水平）+（0.54316 x RP 11 - 110 I1.14的表达水平）+（-0.48794 x CTD-2506 J14.1的表达水平）。Kaplan-Meier分析显示，当将培训、测试和验证队列中的患者分层为高风险或低风险亚组时，与低风险评分的患者相比，高风险评分的患者的总生存期显著降低。多变量生存分析进一步显示，这种4-lncRNA标签是一种新的和重要的预后因素，独立于多个临床病理参数。重要的是，ROC分析表明，该4-lncRNA特征的预测准确性和灵敏度优于那些先前良好建立的预后因素。值得注意的是，在另一个独立的HNSCC队列中，基于通过qRT-PCR定量这些4-lncRNA的预后评分将患者稳健地分层为具有高或低存活率的亚组。综上所述，我们开发了一种用于HNSCC的稳健的4-lncRNA预后特征，其可能为精确肿瘤学提供新的强大的预后生物标志物。
Deregulated long noncoding RNAs (lncRNA) have been critically implicated in tumorigenesis and serve as novel diagnostic and prognostic biomarkers. Here we sought to develop a prognostic lncRNA signature in patients with head and neck squamous cell carcinoma (HNSCC). Original RNA-seq data of 499 HNSCC samples were retrieved from The Cancer Genome Atlas database, which was randomly divided into training and testing set. Univariate Cox regression survival analysis, robust likelihood-based survival model and random sampling iterations were applied to identify prognostic lncRNA candidates in the training cohort. A prognostic risk score was developed based on the Cox coefficient of four individual lncRNA imputed as follows: (0.14546xexpression level of RP11-366H4.1) + (0.27106xexpression level of LINC01123)+(0.54316xexpression level of RP11-110I1.14)+(-0.48794xexpression level of CTD-2506J14.1). Kaplan-Meier analysis revealed that patients with high-risk score had significantly reduced overall survival as compared with those with low-risk score when patients in training, testing, and validation cohorts were stratified into high- or low-risk subgroups. Multivariate survival analysis further revealed that this 4-lncRNA signature was a novel and important prognostic factor independent of multiple clinicopathological parameters. Importantly, ROC analyses indicated that predictive accuracy and sensitivity of this 4-lncRNA signature outperformed those previously well-established prognostic factors. Noticeably, prognostic score based on quantification of these 4-lncRNA via qRT-PCR in another independent HNSCC cohort robustly stratified patients into subgroups with high or low survival. Taken together, we developed a robust 4-lncRNA prognostic signature for HNSCC that might provide a novel powerful prognostic biomarker for precision oncology.