胶质母细胞瘤（GBM）成为最常见的恶性脑肿瘤。组蛋白修饰作为一个表观遗传调控基因表达的机制，与恶性肿瘤密切相关。我们从MSigDB数据库中提取了与组蛋白修饰相关的基因集，并通过AddModuleScore函数进行评分。 Pearson相关分析使用“Hmisc”R软件包中的“rcorr”函数进行。在LASSO Cox分析中筛选出基因。使用TCGA-GBM和CGGA_array_301队列进行模型构建和验证。我们使用微环境细胞人口计数（MCPcounter）、单样本基因集富集分析（ssGSEA）和xCell算法计算了免疫浸润评分。我们利用U87-MG和CHG-5细胞系通过Western blot（WB）评估TMEM176A的表达水平。采用Transwell、EDU、细胞集落形成分析（CFA）和CKK-8实验来研究细胞增殖和迁移率。GBM患者的恶性细胞在TGF-β和低氧途径中表现出明显的活化。组蛋白修饰与GBM中的粘附和神经元发育相关。我们确定了一个包括NBEAL1、AEBP1、TMEM176A、FASTK和CD81五个显著基因的模型，具有预后功效。此外，我们观察到高风险（HR）组中T细胞和CD8阳性T细胞浸润增加。预测5-氟尿嘧啶_1073和Taselisib_1561为GBM患者的潜在治疗选择，而ABT737_1910和Wnt_C59-1622则对HR组的GBM患者表现出更好的反应。在HR组中观察到TP53突变率的上升。TMEM176A在体外调控细胞增殖和迁移方面发挥作用。我们首次提出了基于组蛋白修饰相关基因的新型GBM患者预后模型。此外，我们首次确定了TMEM176A在调控GBM致癌表型中的关键作用。© 2023. 作者授予Springer-Verlag GmbH Germany独家许可，为Springer Nature的一部分。

Glioblastoma (GBM) emerges as the most common malignant brain tumor. Histone modifications, as an epigenetic regulatory mechanism of gene expression, are closely associated with malignant tumors. Gene set related to histone modification was extracted from the MSigDB database, and scored by the function of AddModuleScore. Pearson correlation analysis was utilized using the "rcorr" function of "Hmisc" R package. Genes were screened out using the LASSO Cox analysis. TCGA-GBM and CGGA_array_301 cohorts were employed for constructing model and validation. We calculated immune infiltration scores using microenvironment cell populations counter (MCPcounter), single-sample gene set enrichment analysis (ssGSEA), and xCell algorithms. U87-MG and CHG-5 cell lines were utilized to evaluate expression level of TMEM176A by western blot (WB). Transwell, EDU, colony formation analysis (CFA), and CKK-8 assays were conducted to investigate cell proliferation and migration rate. The malignant cells in GBM patients exhibited notable activation in the TGF-β and hypoxia pathway. Histone modifications were associated with adhesion and neuron development in GBM. We identified a model with five significant genes, namely NBEAL1, AEBP1, TMEM176A, FASTK, and CD81, with prognostic efficacy. Additionally, we observed increased infiltration of T cells and CD8+ T cells in the high-risk (HR) group. 5-Fluorouracil_1073 and Taselisib_1561 were predicted as potential treatment options for GBM patients, while ABT737_1910 and Wnt_C59-1622 exhibited superior response in GBM patients of the HR group. A spike in the TP53 mutation rate was observed in the HR group. TMEM176A played a role in regulating cell proliferation and migration in vitro. We presented a novel prognostic model for patients with GBM, based on histone modification-related genes. In addition, we identified the crucial role of the TMEM176A in the regulation of GBM carcinogenic phenotypes for the first time.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.