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[摘要]
目的:探讨甲基转移酶样蛋白7B(METTL7B)在胶质瘤组织中的表达及其与患者临床病理特征和预后的相关性。方法:基于CGGA数据库胶质瘤数据和GTEx数据库正常脑组织数据,分析METTL7B基因在胶质瘤与正常脑组织中的表达差异,并用GEPIA数据库数据和免疫组织化学染色法进行验证。用Kaplan-Meier生存分析、单因素Cox分析、多因素Cox分析及ROC曲线分析等评估METTL7B在胶质瘤患者预后中的价值,用CGGA数据库数据分析METTL7B表达与胶质瘤患者临床病理特征的相关性,用CIBERSORT及TIMER数据库进行肿瘤免疫细胞浸润分析,进行KEGG通路富集分析及GO功能富集分析,通过基因共表达分析确定与METTL7B相关的基因。结果:METTL7B在胶质瘤组织中明显上调(均P<0.05),METTL7B表达是胶质瘤患者独立的不良预后因素。METTL7B高表达与高龄(>41岁)、肿瘤分级增加、肿瘤复发或继发性肿瘤、IDH野生型、1p19q非共缺失以及肿瘤的恶性病理学有关联(均P<0.01);METTL7B表达与B细胞、CD4+ T细胞、CD8+ T细胞、单核细胞、中性粒细胞、巨噬细胞、活化肥大细胞等免疫细胞有关联(均P<0.05)。KEGG通路富集及GO功能分析结果显示,肿瘤相关信号通路及多种免疫反应在METTL7B高表达表型中显著富集。基因共表达分析结果表明,METTL7B 与 TNFRSF12A、CHI3L1、EMP3 表达呈正相关(r=0.807、0.804、0.783,均 P<0.01),与 ELFN2、REPS2、SHANK2 表达呈负相关(r=-0.642、-0.627、-0.602,均 P<0.01)。结论:METTL7B在胶质瘤组织中的表达上调是预后不良的指标,且与肿瘤免疫浸润相关。
[Key word]
[Abstract]
Objective: To investigate the expression of methyltransferase-like protein 7B (METTL7B) in glioma tissues and its correlation with clinicopathological features and prognosis of patients. Methods: The differential expression of METTL7B gene in glioma and normal brain tissues was analyzed based on the glioma data in CGGA database and the normal brain tissue data in the GTEx database, which was verified using the GEPIA database and immunohistochemical staining. Kaplan-Meier survival analysis, univariate and multivariate Cox analyses and ROC curve analysis were used to evaluate the prognostic value of METTL7B for the patients with glioma. CGGA database was used to analyze the correlation between the METTL7B expression and the clinicopathological characteristics of patients with glioma. CIBERSORT and TIMER databases were adopted to analyze the tumor immune cell infiltration.The genes closely related to METTL7B were identified through gene co-expression analysis. KEGG pathway enrichment analysis and GO function enrichment analysis were also performed. Results: METTL7B was significantly upregulated in glioma tissues (all P<0.05), and its high expression was an independent adverse prognostic factor for glioma patients. High METTL7B expression was significantly related to old age (>41 years old), advanced tumor grade, tumor recurrence or secondary tumors, IDH wild-type, 1p19q non-codeletion and tumor malignant pathology (all P<0.01). METTL7B expression was related to immune cells, such as B cells, CD4+T cells, CD8+ T cells, monocytes, neutrophils, macrophages, and activated mast cells (all P<0.05). The KEGG pathway enrichment and the GO function analysis showed that tumor-related signaling pathways and multiple immune responses were significantly enriched in the METTL7B high expression phenotypes (all P<0.05). Gene co-expression analysis results showed that METTL7B expression was positively correlated with the expression of TNFRSF12A, CHI3L1 and EMP3 (r=0.807, 0.804, 0.783, all P<0.01), but negatively correlated with the expression of ELFN2, REPS2, and SHANK2 (r=-0.642,-0.627,-0.602, all P<0.01). Conclusion: The upregulation of METTL7B expression in glioma tissues is an indicator of poor prognosis, which is related to tumor immune infiltration.
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[基金项目]
国家重点研发计划资助项目(No. 2017YFC0108803);国家自然科学基金资助项目(No. 81801667)