Identification of lncRNA Signature of Tumor-Infiltrating T Lymphocytes With Potential Implications for Prognosis and Chemotherapy of Head and Neck Squamous Cell Carcinoma.
Identification of lncRNA Signature of Tumor-Infiltrating T Lymphocytes With Potential Implications for Prognosis and Chemotherapy of Head and Neck Squamous Cell Carcinoma.
复制标题
肿瘤浸润 T 淋巴细胞 lncRNA 特征的鉴定对头颈鳞状细胞癌的预后和化疗具有潜在意义
DOI：
10.3389/fphar.2021.795205
复制
发表时间：
2021
影响因子：
5.6
通讯作者：
Pan Y
中科院分区：
文献类型：
--
作者：
Wang L;Yang G;Liu G;Pan Y
目的：我们系统分析了HNSCC浸润性T淋巴细胞lncRNA（HILTlncRNA），以评估其对抗程序性死亡-1（PD-1）治疗患者的生存结局和免疫治疗反应的预测价值，并评估其对化疗药物的预测能力。 方法：从癌症基因组图谱（TCGA）数据库中获得HNSCC转录组和临床信息。免疫细胞微阵列数据从基因表达综合数据库（GEO）获得。通过差异表达分析鉴定T细胞特异性lncRNA。通过单变量cox、lasso和多变量cox回归分析过滤并建模预后配对的HILTlncRNA（PHILTlncRNA）。为了构建lncRNA-miRNA-mRNA竞争性内源性RNA（ceRNA）调控网络，整合HNSCC患者差异表达的mRNA，基于miRcode、miRDB、miRTarBase和TargetScan数据库筛选与T细胞特异性lncRNA相互作用的microRNA和差异表达的mRNA。 结果：共鉴定出75个T细胞特异性lncRNA和9个预测性PHILTlncRNA。低风险HNSCC患者预后较好，免疫细胞浸润显著，驱动免疫应答。RNA结合蛋白（RBP）、PD-1和程序性细胞死亡1配体1（PD-L1）的差异表达在HNSCC患者的高风险组和低风险组中得到证实。在高风险组中，PD-1的高表达改善了患者的预后，而在低风险组中观察到相反的情况。与正常对照组相比，两种RBP（DNMT1和ZC3H12D）基因启动子区甲基化水平在HNSCC患者中均降低，其表达水平与PD-1、PD-L1水平及T细胞浸润呈正相关。最后，我们筛选了HNSCC患者对化疗药物的敏感性，发现高风险组和低风险组之间存在差异。 结论：HILTlncRNAs为免疫靶向治疗和药物开发提供了理论基础。
Purpose: We systematically analyzed HNSCC-infiltrating T lymphocytes lncRNAs (HILTlncRNAs) to assess their predictive value for the survival outcome and immunotherapy response of patients with anti-programmed death-1 (PD-1) therapy and to evaluate their predictive power to chemotherapeutic agents. Methods: HNSCC transcriptome and clinical information was obtained from The Cancer Genome Atlas (TCGA) database. Immunocell microarray data were obtained from the Gene Expression Omnibus (GEO) database. T-cell-specific lncRNAs were identified by differential expression analysis. Prognostic paired HILTlncRNAs (PHILTlncRNAs) were filtered and modeled by univariate cox, lasso and multivariate cox regression analysis. To construct lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) regulatory networks, differentially expressed mRNAs in HNSCC patients were incorporated, microRNAs and differentially expressed mRNAs interacting with T-cell-specific lncRNAs were filtered out based on miRcode, miRDB, miRTarBase, and TargetScan databases. Results: 75 T-cell-specific lncRNAs and 9 prognostic PHILTlncRNAs were identified. Low-risk HNSCC patients had a better prognosis and significant immune cell infiltration, driving the immune response. Differential expression of RNA-binding proteins (RBPs), PD-1 and programmed cell death 1 ligand 1 (PD-L1) was demonstrated in the high and low risk groups of HNSCC patients. In the high risk group, high expression of PD-1 improved patient prognosis, whereas the opposite was observed in the low-risk group. The promoter methylation levels of two RBPs (DNMT1 and ZC3H12D) were decreased in HNSCC patients compared with normal samples, their expression levels were positively correlated with PD-1 and PD-L1 levels and T-cell infiltration. Finally, we screened the sensitivity of HNSCC patients to chemotherapeutic agents and found it differed between high and low risk groups. Conclusion: HILTlncRNAs provided a theoretical basis for immune targeted therapy and drug development.
登录
查看更多内容
阻断 TIM3 可通过减少头颈癌中的调节性 T 细胞来缓解免疫抑制
DOI：
10.1186/s13046-018-0713-7
发表时间：
2018-03-05
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Liu JF;Wu L;Yang LL;Deng WW;Mao L;Wu H;Zhang WF;Sun ZJ
通讯作者：
Sun ZJ
影响因子：
11.2
作者：
Gomez KE;Wu F;Keysar SB;Morton JJ;Miller B;Chimed TS;Le PN;Nieto C;Chowdhury FN;Tyagi A;Lyons TR;Young CD;Zhou H;Somerset HL;Wang XJ;Jimeno A
通讯作者：
Jimeno A
影响因子：
3.7
作者：
Kross, K. W.;Heimdal, J. H.;Aarstad, H. J.
通讯作者：
Aarstad, H. J.
肿瘤基质中 CD68( ) 肿瘤相关巨噬细胞的微定位与口腔鳞状细胞癌患者不良临床结果相关
影响因子：
--
作者：
Ni, Yan-Hong;Ding, Liang;Hou, Ya-Yi
通讯作者：
Hou, Ya-Yi
影响因子：
4
作者：
Diao, Pengfei;Song, Yue;Cheng, Jie
通讯作者：
Cheng, Jie