Supplementary Material for: Prognostic Potential of METTL7B in Glioma

Objective: Methyltransferase-like 7B (METTL7B) is a member of methyltransferase-like family. Little is known about the exact role of METTL7B in cancer. This study aims to investigate the role of METTL7B in gliomas. Methods: The expression of METTL7B in glioma and adjacent normal tissues were examined by using TCGA, Chinese Glioma Genome Atlas (CGGA) database, and clinical tissues. Results: The results showed that METTL7B was highly expressed in glioma. Patients with high levels of METTL7B usually had poor survival in glioma, especially in low-grade glioma (LGG). Data from CGGA showed that METTL7B was an independent risk factor of glioma and can be used to evaluate the survival time of glioma patients. Hypomethylation in the METTL7B CpG islands was lower in LGG, and all the hypomethylated METTL7B islands were correlated with poor LGG survival. Furthermore, METTL7B levels were correlated with high numbers of tumor infiltrated immune cells in glioma, especially in LGG. ). Gene Set Enrichment Analysis found METTL7B was correlated with leukocyte proliferation, T-cell proliferation, peptidase activity, lymphocyte activation, etc. TCGA and CGGA database analysis showed that there were 1,546 and 1,117 genes that had a synergistic effect with METTL7B in glioma, respectively, and there were 372 genes overlapped between the 2 groups, including PD-L1. Data from clinical tissues also showed PD-L1 was highly expressed in glioma tissues and was positively correlated with METTL7B. Conclusion: Our study suggested that METTL7B was a potential prognostic biomarker for glioma and other cancers, and it may act as an oncogenic driver and may be a potential therapeutic target in human cancer, especially in LGG.

目的：甲基转移酶样7B（Methyltransferase-like 7B, METTL7B）属于甲基转移酶样家族成员，目前学界对其在癌症中的确切功能仍知之甚少。本研究旨在探讨METTL7B在神经胶质瘤中的作用。
方法：通过癌症基因组图谱（The Cancer Genome Atlas, TCGA）、中国神经胶质瘤基因组图谱（Chinese Glioma Genome Atlas, CGGA）数据库及临床组织样本，检测METTL7B在神经胶质瘤组织与配对癌旁正常组织中的表达水平。
结果：结果显示，METTL7B在神经胶质瘤组织中呈高表达状态。METTL7B高表达的神经胶质瘤患者通常预后不良，尤其在低级别胶质瘤（low-grade glioma, LGG）患者中更为显著。CGGA数据库分析结果表明，METTL7B是神经胶质瘤的独立危险因素，可用于评估神经胶质瘤患者的生存时长。METTL7B基因CpG岛的低甲基化水平在低级别胶质瘤中更低，且所有低甲基化的METTL7B CpG岛均与低级别胶质瘤患者的不良预后相关。此外，神经胶质瘤组织中METTL7B的表达水平与肿瘤浸润免疫细胞数量呈正相关，该关联在低级别胶质瘤中尤为突出。基因集富集分析（Gene Set Enrichment Analysis, GSEA）结果显示，METTL7B与白细胞增殖、T细胞增殖、肽酶活性、淋巴细胞活化等生物学过程密切相关。对TCGA和CGGA数据库的分析显示，分别有1546个和1117个基因在神经胶质瘤中与METTL7B存在协同调控效应，两组间共有372个重叠基因，其中包括程序性死亡受体配体1（PD-L1）。临床组织样本数据同样证实，PD-L1在神经胶质瘤组织中呈高表达，且与METTL7B的表达水平呈正相关。
结论：本研究表明，METTL7B可作为神经胶质瘤及其他癌症的潜在预后生物标志物，其可能作为致癌驱动因子，有望成为人类癌症尤其是低级别胶质瘤的潜在治疗靶点。