Deng Yaping, Li Kehua, Tan Fengwu, Liu Hanbo
Department of Otolaryngology Head and Neck surgery, The Affiliated Zhuzhou Hospital Xiangya Medical College CSU, ZhuZhou, Hunan, China.
J Oncol. 2021 Aug 20;2021:1814266. doi: 10.1155/2021/1814266. eCollection 2021.
Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive solid tumor. Because most studies have focused on the intrinsic carcinogenic pathways of tumors, we focused on the relationship between N6-methyladenosine (m6A) and the prognosis of HNSCC in the tumor immune microenvironment. We downloaded RNA-seq data from the TCGA dataset and used univariate Cox regression to screen m6A-related lncRNAs. The expression value of LASSO-screened genes was the sum of LASSO regression coefficients. We then evaluated relationships between the risk score and cellular components or cellular immune response. Differences in immune response under various algorithms were visualized with heat maps. The GSVA package in R was used to analyze GO, BP, KEGG, and hallmark gene sets of immune checkpoint clusters and immune checkpoint scores. The GSEA analysis was performed with the cluster profile package, yielding 21 m6A genes. Related lncRNAs were screened with Pearson's correlations, and the resulting 442 lncRNAs were screened using single-factor analysis. Eight lncRNAs closely related to prognosis were identified through survival random forest. Survival analysis showed that patients with a high risk score had a poor prognosis. Low- and high-risk-score groups differed significantly in m6A gene expression. Prognostic scores from different algorithms were significantly correlated with B cells, T cells, and memory cells in the immune microenvironment. Expression of immune checkpoints and signal pathways differed significantly across risk-score groups, suggesting that m6A could mediate lncRNA-induced immune system dysfunction and affect HNSCC development. A comprehensive study of tumor-cell immune characteristics should provide more insight into the complex immune microenvironment, thus contributing to the development of new immunotherapeutic agents.
头颈部鳞状细胞癌(HNSCC)是一种侵袭性很强的实体瘤。由于大多数研究都集中在肿瘤的内在致癌途径上,我们聚焦于肿瘤免疫微环境中N6-甲基腺苷(m6A)与HNSCC预后的关系。我们从TCGA数据集中下载了RNA测序数据,并使用单变量Cox回归筛选与m6A相关的长链非编码RNA(lncRNA)。经LASSO筛选的基因的表达值为LASSO回归系数之和。然后,我们评估了风险评分与细胞成分或细胞免疫反应之间的关系。通过热图直观显示了各种算法下免疫反应的差异。使用R语言中的GSVA软件包分析免疫检查点簇和免疫检查点评分的基因本体(GO)、生物学过程(BP)、京都基因与基因组百科全书(KEGG)和特征基因集。使用clusterProfiler软件包进行基因集富集分析(GSEA),得到21个m6A基因。通过Pearson相关性筛选相关lncRNA,并使用单因素分析对得到的442个lncRNA进行筛选。通过生存随机森林鉴定出8个与预后密切相关的lncRNA。生存分析表明,高风险评分的患者预后较差。低风险评分组和高风险评分组在m6A基因表达上存在显著差异。不同算法的预后评分与免疫微环境中的B细胞、T细胞和记忆细胞显著相关。免疫检查点和信号通路的表达在不同风险评分组之间存在显著差异,这表明m6A可能介导lncRNA诱导的免疫系统功能障碍并影响HNSCC的发展。对肿瘤细胞免疫特征进行全面研究应能更深入了解复杂的免疫微环境,从而有助于开发新的免疫治疗药物。