The Prognostic Value and Immune Landscapes of a m(6)A/m(5)C/m(1)A-Related LncRNAs Signature in Head and Neck Squamous Cell Carcinoma.
The Prognostic Value and Immune Landscapes of a m(6)A/m(5)C/m(1)A-Related LncRNAs Signature in Head and Neck Squamous Cell Carcinoma.
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DOI：
10.3389/fcell.2021.718974
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发表时间：
2021
影响因子：
5.5
通讯作者：
Xiao H
中科院分区：
文献类型：
--
作者：
Wang E;Li Y;Ming R;Wei J;Du P;Zhou P;Zong S;Xiao H
背景资料：N6-甲基腺苷（m6 A）、5-甲基胞嘧啶（m5 C）和N1-甲基腺苷（m1A）是参与癌症进展的主要RNA甲基化修饰。然而，m6 A/m5 C/m1A相关的长链非编码RNA（lncRNA）是否影响头颈部鳞状细胞癌（HNSCC）的预后仍不清楚。 研究方法：我们总结了52个m6 A/m5 C/m1A相关基因，从癌症基因组图谱（TCGA）数据库下载了44个正常样本和501个HNSCC肿瘤样本的RNA-seq数据和临床信息，然后搜索m6 A/m5 C/m1A相关基因共表达的lncRNA。我们采用最小绝对收缩和选择算子（LASSO）考克斯回归获得m6 A/m5 C/m1 A相关的lncRNA，以构建HNSCC的预后特征。 结果：该预后特征基于六种m6 A/m5 C/m1A相关的lncRNA（AL035587.1、AC009121.3、AF131215.5、FMR 1-IT 1、AC106820.5、PTOV 1-AS 2）。结果发现，高风险亚组的总生存率（OS）低于低风险亚组。而且，结果显示大多数免疫检查点基因在两个危险组之间存在显著差异（p <0. 05）。免疫微环境分析显示，低危组NK细胞静息、巨噬细胞M2和中性粒细胞含量显著低于高危组（p < 0.05），而B细胞、浆细胞和调节性T细胞含量则相反（p < 0.05）。此外，高肿瘤突变负荷（TMB）患者的总体生存率低于低肿瘤突变负荷患者。 结论：m6 A/m5 C/m1A相关lncRNAs与HNSCC的预后、免疫微环境及TMB的关系。这些m6 A/m5 C/m1A相关的lncRNA有可能成为HNSCC免疫治疗的新选择。
Background: N6-methyladenosine (m6A), 5-methylcytosine (m5C) and N1-methyladenosine (m1A) are the main RNA methylation modifications involved in the progression of cancer. However, it is still unclear whether m6A/m5C/m1A-related long non-coding RNAs (lncRNAs) affect the prognosis of head and neck squamous cell carcinoma (HNSCC). Methods: We summarized 52 m6A/m5C/m1A-related genes, downloaded 44 normal samples and 501 HNSCC tumor samples with RNA-seq data and clinical information from The Cancer Genome Atlas (TCGA) database, and then searched for m6A/m5C/m1A-related genes co-expressed lncRNAs. We adopt the least absolute shrinkage and selection operator (LASSO) Cox regression to obtain m6A/m5C/m1A-related lncRNAs to construct a prognostic signature of HNSCC. Results: This prognostic signature is based on six m6A/m5C/m1A-related lncRNAs (AL035587.1, AC009121.3, AF131215.5, FMR1-IT1, AC106820.5, PTOV1-AS2). It was found that the high-risk subgroup has worse overall survival (OS) than the low-risk subgroup. Moreover, the results showed that most immune checkpoint genes were significantly different between the two risk groups (p < 0.05). Immunity microenvironment analysis showed that the contents of NK cell resting, macrophages M2, and neutrophils in samples of low-risk group were significantly lower than those of high-risk group (p < 0.05), while the contents of B cells navie, plasma cells, and T cells regulatory (Tregs) were on the contrary (p < 0.05). In addition, patients with high tumor mutational burden (TMB) had the worse overall survival than those with low tumor mutational burden. Conclusion: Our study elucidated how m6A/m5C/m1A-related lncRNAs are related to the prognosis, immune microenvironment, and TMB of HNSCC. In the future, these m6A/m5C/m1A-related lncRNAs may become a new choice for immunotherapy of HNSCC.
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