Li Rui, Yin Yun-Hong, Ji Xiu-Li, Liu Xiao, Li Jian-Ping, Qu Yi-Qing
Department of Pulmonary and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Department of Pulmonary and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China.
Front Mol Biosci. 2021 Jun 4;8:644620. doi: 10.3389/fmolb.2021.644620. eCollection 2021.
N6-methyladenosine RNA modification plays a significant role in the progression of multiple tumorigenesis. Our study identified the imperative role of m6A regulators in the tumor immune microenvironment, survival, stemness score, and anticancer drug sensitivity of pan-cancer. The Wilcox test was to identify the differential expression between 17 m6A regulators across 33 TCGA cancer types and their normal tissues from UCSC Xena GDC pan-cancer. Survival analysis of m6A-related regulators in 33 TCGA cancer types was identified using the "survival" and "survminer" package. The Spearman correlation test and Pearson correlation test were used to identify the correlation relationship between m6A regulators expression and tumor microenvironment, tumor stem cell score, and drug sensitivity of anticancer drugs. ConsensusPathDB was used for exploring m6A regulators functional enrichment. The 17 (METTL3, WTAP, METTL14, RBM15, RBM15B, VIRMA, HNRNPC, HNRNPA2B1, YTHDC1, ZC3H13, YTHDF1, YTHDC2, YTHDF2, IGF2BP3, IGF2BP1, FTO, and ALKBH5) m6A regulators were differentially expressed in 18 TCGA cancer types and adjacent normal tissues. Correlation analysis indicated that the relationship between the expression of 17 m6A regulators and tumor microenvironment indicated that the higher expression of m6A regulators, the higher the degree of tumor stem cells. The anticancer drug sensitivity analysis indicated that ZC3H13 expression had a positive relationship with anticancer drugs such as selumetinib, dabrafenib, cobimetinib, trametinib, and hypothemycin ( < 0.001). YTHDF2 expression was significantly negatively correlated with the anticancer drug dasatinib ( < 0.001). The pan-cancer immune subtype analysis showed that the 17 m6A regulators were significantly different in immune subtype C1 (wound healing), C3 (inflammatory), C2 (IFN-gamma dominant), C5 (immunological quiet), C4 (lymphocyte depleted), and C6 (TGF-beta dominant) ( < 0.001). Our study provides a comprehensive insight for revealing the significant role of m6A regulators in the tumor immune microenvironment, stemness score, and anticancer drug sensitivity of human cancers.
N6-甲基腺苷（m6A）RNA修饰在多种肿瘤发生发展过程中发挥着重要作用。我们的研究确定了m6A调控因子在泛癌的肿瘤免疫微环境、生存、干性评分和抗癌药物敏感性中的关键作用。采用Wilcox检验来确定来自UCSC Xena GDC泛癌数据中33种TCGA癌症类型及其正常组织中17种m6A调控因子的差异表达。使用“survival”和“survminer”软件包对33种TCGA癌症类型中的m6A相关调控因子进行生存分析。采用Spearman相关检验和Pearson相关检验来确定m6A调控因子表达与肿瘤微环境、肿瘤干细胞评分及抗癌药物敏感性之间的相关性。利用ConsensusPathDB探索m6A调控因子的功能富集情况。这17种（METTL3、WTAP、METTL14、RBM15、RBM15B、VIRMA、HNRNPC、HNRNPA2B1、YTHDC1、ZC3H13、YTHDF1、YTHDC2、YTHDF2、IGF2BP3、IGF2BP1、FTO和ALKBH5）m6A调控因子在18种TCGA癌症类型及其癌旁正常组织中存在差异表达。相关性分析表明，17种m6A调控因子的表达与肿瘤微环境之间的关系显示，m6A调控因子表达越高，肿瘤干细胞程度越高。抗癌药物敏感性分析表明，ZC3H13的表达与司美替尼、达拉非尼、考比替尼、曲美替尼和hypothemycin（<0.001）等抗癌药物呈正相关。YTHDF2的表达与抗癌药物达沙替尼呈显著负相关（<0.001）。泛癌免疫亚型分析显示，这17种m6A调控因子在免疫亚型C1（伤口愈合）、C3（炎症）、C2（IFN-γ主导）、C5（免疫静息）、C4（淋巴细胞耗竭）和C6（TGF-β主导）中存在显著差异（<0.001）。我们的研究为揭示m6A调控因子在人类癌症的肿瘤免疫微环境、干性评分和抗癌药物敏感性中的重要作用提供了全面的见解。
