Identification of tumor immune infiltration-associated lncRNAs for improving prognosis and immunotherapy response of patients with non-small cell lung cancer
Identification of tumor immune infiltration-associated lncRNAs for improving prognosis and immunotherapy response of patients with non-small cell lung cancer
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DOI：
10.1136/jitc-2019-000110
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发表时间：
2020-01-01
影响因子：
10.9
通讯作者：
Zhou, Meng
中科院分区：
文献类型：
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作者：
Sun, Jie;Zhang, Zicheng;Zhou, Meng
越来越多的证据表明长链非编码RNA（lncRNA）与非小细胞肺癌（NSCLC）的免疫调节和肿瘤微环境的功能相关。然而，肿瘤免疫浸润相关的lncRNA及其在改善临床结果和免疫治疗中的价值仍然在很大程度上未被探索。方法我们开发了一种计算方法，通过对115种免疫细胞系的lncRNA，免疫和临床特征的综合分析，187个NSCLC细胞系和1533名NSCLC患者。结果计算免疫分析和lncRNA谱分析证实了一个由7个lncRNA组成的与肿瘤免疫浸润相关的lncRNA标签（TILSig）。TILSig在训练和验证队列中将患者显著分层为免疫冷组和免疫热组。与免疫冷患者相比，这些免疫热患者表现出显著改善的生存结局和更大的免疫细胞浸润。多因素分析显示，在调整其他临床因素后，TILSig是一个独立的预测因素。解释TILSig和免疫检查点基因的进一步分析显示，TILSig在具有相似免疫检查点基因表达水平的患者中具有区分能力，并且观察到具有低TILSig和低免疫检查点基因表达的患者的生存期显著延长，这意味着对免疫检查点抑制剂（ICI）的反应更好。结论我们的发现证明了lncRNA在评估肿瘤免疫浸润方面的重要性和价值，并强调了lncRNA与特异性免疫检查点因子结合作为预测生物标志物的潜力ICI反应，以便更精确地选择患者。
Background Increasing evidence has demonstrated the functional relevance of long non-coding RNAs (lncRNAs) to immunity regulation and the tumor microenvironment in non-small cell lung cancer (NSCLC). However, tumor immune infiltration-associated lncRNAs and their value in improving clinical outcomes and immunotherapy remain largely unexplored.Methods We developed a computational approach to identify an lncRNA signature (TILSig) as an indicator of immune cell infiltration in patients with NSCLC through integrative analysis for lncRNA, immune and clinical profiles of 115 immune cell lines, 187 NSCLC cell lines and 1533 patients with NSCLC. Then the influence of the TILSig on the prognosis and immunotherapy in NSCLC was comprehensively investigated.Results Computational immune and lncRNA profiling analysis identified an lncRNA signature (TILSig) consisting of seven lncRNAs associated with tumor immune infiltration. The TILSig significantly stratified patients into the immune-cold group and immune-hot group in both training and validation cohorts. These immune-hot patients exhibit significantly improved survival outcome and greater immune cell infiltration compared with immune-cold patients. Multivariate analysis revealed that the TILSig is an independent predictive factor after adjusting for other clinical factors. Further analysis accounting for TILSig and immune checkpoint gene revealed that the TILSig has a discriminatory power in patients with similar expression levels of immune checkpoint genes and significantly prolonged survival was observed for patients with low TILSig and low immune checkpoint gene expression implying a better response to immune checkpoint inhibitor (ICI) immunotherapy.Conclusions Our finding demonstrated the importance and value of lncRNAs in evaluating the immune infiltrate of the tumor and highlighted the potential of lncRNA coupled with specific immune checkpoint factors as predictive biomarkers of ICI response to enable a more precise selection of patients.