在原发性脑肿瘤中，胶质瘤与不良预后相关，并且中位生存期因肿瘤分级和亚型而异。作为胶质瘤中最恶性的形式，胶质母细胞瘤（GBM）构成了重要的健康问题。已经证明，颗粒素（GRN）的改变是一些疾病的原因。然而，GRN与GBM之间的关系仍不清楚。我们通过癌症基因组图谱（TCGA）数据库评估了GRN在GBM中的作用。首先，我们通过GEPIA数据库评估了GRN与GBM之间的关系。接下来，通过逻辑回归和多元Cox分析方法分析了GRN与GBM预后之间的关系。我们还利用CIBERSORT和GEPIA相关模块研究了癌症中GRN与免疫浸润之间的联系。使用TCGA数据，进行了基因集富集分析（GSEA）。我们还利用肿瘤免疫评估资源（TIMER）检查了GRN表达和免疫浸润水平在GBM中的数据集，并研究了GBM中的累积生存率。最后，我们通过Western blotting、RT-qPCR和免疫组织化学验证了来自GBM患者的组织。通过逻辑回归的单因素研究，显示GRN表达增加与肿瘤分级显著相关。此外，多元回归分析揭示了GRN表达下调是有利预后的独立预测因素。GRN表达水平与浸润GBM的CD4+ T细胞、中性粒细胞、巨噬细胞和树突状细胞（DC）的数量呈正相关。GSEA还发现，高GRN表达表型途径富集了与免疫应答分子介导物的生产、淋巴细胞介导的免疫、细胞因子介导的信号转导途径、白细胞增殖、细胞趋化和CD4+ alpha beta T细胞的激活有关的基因。在基因组物质代谢通路，Kyoto的基因与基因组百科全书（KEGG）中富集的不同途径包括溶酶体、细胞凋亡、原发性免疫不良、趋化因子信号通路、自然杀伤细胞介导的细胞毒作用和B细胞受体信号通路。验证结果表明，GRN在GBM组织中上调。这些结果表明，GRN是GBM状态的潜在指标。GRN是一种预后生物标记物，并与GBM中的免疫浸润相关。版权所有 © 2023 Xu、Xiao、Hu、Zhong、Zeng、Wu、Li和Song。

Among primary brain tumors, gliomas are associated with a poor prognosis and a median survival that varies depending on the tumor grade and subtype. As the most malignant form of glioma, glioblastoma (GBM) constitutes a significant health concern. Alteration in granulin(GRN) has been proved to be accountable for several diseases. However, the relationship between GRN and GBM remains unclear. We evaluated the role of GRN in GBM through The Cancer Genome Atlas (TCGA) database.First, we assessed the relationship between GRN and GBM through the GEPIA database. Next, the relationship between GRN and GBM prognosis was analyzed by logistic regression and multivariate cox methods. Using CIBERSORT and the GEPIA correlation module, we also investigated the link between GRN and immune infiltrates in cancer. Using the TCGA data, a gene set enrichment analysis (GSEA) was performed. We also employed Tumor Immune Estimation Resource (TIMER) to examine the data set of GRN expression and immune infiltration level in GBM and investigate the cumulative survival in GBM. We also validated tissues from GBM patients by Western blotting, RT-qPCR, and immunohistochemistry.Increased GRN expression was shown to have a significant relationship to tumor grade in a univariate study utilizing logistic regression. Furthermore, multivariate analysis disclosed that GRN expression down-regulation is an independent predictive factor for a favorable outcome. GRN expression level positively correlates with the number of CD4+ T cells, neutrophils, macrophages, and dendritic cells (DCs) that infiltrate a GBM. The GSEA also found that the high GRN expression phenotype pathway was enriched for genes involved in immune response molecular mediator production, lymphocyte-mediated immunity, cytokine-mediated signaling pathway, leukocyte proliferation, cell chemotaxis, and CD4+ alpha beta T cell activation. Differentially enriched pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) include lysosome, apoptosis, primary immunodeficiency, chemokine signaling pathway, natural killer cell-mediated cytotoxicity, and B cell receptor signaling pathway. Validated result showed that GRN was upregulated in GBM tissues. These results suggested that GRN was a potential indicator for the status of GBM.GRN is a prognostic biomarker and correlated with immune infiltrates in GBM.Copyright © 2023 Xu, Xiao, Hu, Zhong, Zeng, Wu, Li and Song.