m^(7)G甲基转移酶1与泛癌预后及免疫浸润关联的初步分析

Preliminary analysis of association of m^(7)G methyltransferase 1 with pan-cancer prognosis and immune infiltration

目的:探讨多种类型肿瘤中RNA m^(7)G甲基转移酶1(METTL1)表达规律及其与预后、免疫浸润的关联,以期为癌症生物标志物的筛选及其发生、发展机制提供新的参考依据。方法:运用癌症基因组图谱(TCGA)分析33种肿瘤中METTL1 mRNA表达谱及肿瘤组与正常对照组METTL1表达差异;Cox回归模型和Kaplan-Meier探讨METTL1表达与癌症患者预后的相关性;分析肝细胞癌(LIHC)中METTL1表达与免疫浸润的关联,并结合荧光定量PCR初步验证正常肝细胞和肝癌细胞中METTL1与免疫检查点的mRNA表达水平。结果:METTL1在癌组织和癌旁组织表达水平存在差异,在大多数癌组织中呈高表达;METTL1高表达显著缩短脑低级别胶质瘤(LGG)、LIHC和间皮瘤(MESO)患者中位生存时间;LIHC中METTL1表达与多种炎症细胞水平呈正相关关系,且METTL1表达水平与免疫检测点LAG3和PDCD1表达呈正相关关系(P<0.001),这与其在体外培养的肝癌细胞中mRNA表达水平一致。结论:METTL1显著促进大多数肿瘤的发生和进展,其负向调控LGG、LIHC以及MESO患者的预后生存率,并与免疫浸润呈正相关关系,有望作为基于LAG3和PDCD1免疫治疗的癌症生物标志物。

Objective:To investigate the expression of RNA m^(7)G methyltransferase 1(METTL1)in various types of tumors and its association with prognosis and immune infiltration,in order to provide a new reference for the screening of cancer biomarkers and their mechanisms of occurrence and development.Methods:The Cancer Ge-nome Atlas(TCGA)was used to analyze the mRNA expression profile of METTL1 in 33 tumors and the differ-ences in METTL1 expression between the tumor group and the normal control group.Cox regression model and Kaplan-Meier were used to analyze the correlation between METTL1 expression and the prognosis of cancer pa-tients.The association between METTL1 expression and immune infiltration in liver hepatocellular carcinoma(LIHC)was analyzed,and the mRNA expression levels of METTL1 and immune checkpoint in normal hepato-cytes and LIHC cells were preliminatively verified by fluorescence quantitative PCR.Results:The expression level of METTL1 was different between cancer tissues and adjacent tissues,and it was highly expressed in most cancer tissues.High expression of METTL1 significantly shortened the median survival time of patients with low grade glioma(LGG),LIHC and mesothelioma(MESO).The expression level of METTL1 in LIHC was positively correlated with the levels of multiple inflammatory cells.And the expression level of METTL1 was positively cor-related with the expression of immune checkpoints LAG3 and PDCD1(P<0.001),which was consistent with the mRNA expression level in cultured LIHC cells in vitro.Conclusion:METTL1 significantly promotes the occur-rence and progression of most tumors,negatively regulates the prognosis survival rate of LGG,LIHC and MESO patients,and is positively correlated with immune infiltration.METTL1 is expected to be a cancer biomarker based on LAG3 and PDCD1 immunotherapy.