Zhang Xiangsheng, Zhong Liye, Zou Zhilin, Liang Guosheng, Tang Zhenye, Li Kai, Tan Shuzhen, Huang Yongmei, Zhu Xiao
The Marine Biomedical Research Institute of Guangdong Zhanjiang, Guangdong Medical University, Zhanjiang, China.
Department of Hematology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Front Oncol. 2021 Mar 18;11:623170. doi: 10.3389/fonc.2021.623170. eCollection 2021.
N6-methyladenosine (m6A) is one of the most active modification factors of mRNA, which is closely related to cell proliferation, differentiation, and tumor development. Here, we explored the relationship between the pathogenesis of hematological malignancies and the clinicopathologic parameters. The datasets of hematological malignancies and controls were obtained from the TCGA [AML (n = 200), DLBCL (n = 48)] and GTEx [whole blood (n = 337), blood vascular artery (n = 606)]. We analyzed the m6A factor expression differences in normal tissue and tumor tissue and their correlations, clustered the express obvious clinical tumor subtypes, determined the tumor risk score, established Cox regression model, performed univariate and multivariate analysis on all datasets. We found that the AML patients with high expression of IGF2BP3, ALKBH5, and IGF2BP2 had poor survival, while the DLBCL patients with high expression of METTL14 had poor survival. In addition, "Total" datasets analysis revealed that IGF2BP1, ALKBH5, IGF2BP2, RBM15, METTL3, and ZNF217 were potential oncogenes for hematologic system tumors. Collectively, the expressions of some m6A regulators are closely related to the occurrence and development of hematologic system tumors, and the intervention of specific regulatory factors may lead to a breakthrough in the treatment in the future.
N6-甲基腺苷(m6A)是信使核糖核酸(mRNA)最活跃的修饰因子之一,与细胞增殖、分化及肿瘤发展密切相关。在此,我们探究了血液系统恶性肿瘤的发病机制与临床病理参数之间的关系。血液系统恶性肿瘤和对照的数据集来自癌症基因组图谱(TCGA)[急性髓系白血病(AML,n = 200),弥漫性大B细胞淋巴瘤(DLBCL,n = 48)]和基因型组织表达(GTEx)[全血(n = 337),血管动脉(n = 606)]。我们分析了正常组织和肿瘤组织中m6A因子的表达差异及其相关性,对表达明显的临床肿瘤亚型进行聚类,确定肿瘤风险评分,建立Cox回归模型,对所有数据集进行单因素和多因素分析。我们发现,胰岛素样生长因子2结合蛋白3(IGF2BP3)、ALK蛋白家族成员5(ALKBH5)和胰岛素样生长因子2结合蛋白2(IGF2BP2)高表达的AML患者生存较差,而METTL14高表达的DLBCL患者生存较差。此外,“总计”数据集分析显示,胰岛素样生长因子2结合蛋白1(IGF2BP1)、ALKBH5、IGF2BP2、RNA结合基序蛋白15(RBM15)、甲基转移酶样3(METTL3)和锌指蛋白217(ZNF217)是血液系统肿瘤的潜在癌基因。总的来说,一些m6A调节因子的表达与血液系统肿瘤的发生发展密切相关,特定调节因子的干预可能在未来治疗中带来突破。