Gliomas are highly heterogeneous brain tumours that are resistant to therapies. The molecular signatures of gliomas play a high-ranking role in tumour prognosis and treatment. In addition, patients with gliomas with a mesenchymal phenotype manifest overpowering immunosuppression and sophisticated resistance to treatment. Thus, studies on gene/protein coexpression networks and hub genes in gliomas holds promise in determining effective treatment strategies. Therefore, in this study, we aimed to. Using average linkage hierarchical clustering, 13 modules and 224 hub genes were described. Top ten hub genes (CLIC1, EMP3, TIMP1, CCDC109B, CASP4, MSN, ANXA2P2, CHI3L1, TAGLN2, S100A11), selected from the most meaningful module, were associated with poor prognosis. String analysis, co-immunoprecipitation and immunofluorescence revealed a significant correlation between TIMP1 and CHI3L1. Furthermore, we found, both in vivo and in vitro, that TIMP1 promoted gliomagenesis via CHI3L1 overexpression as well as NF-κB activation. TIMP1 expression correlated with tumour immune infiltration and immune checkpoint-related gene expression. In addition, TIMP1 resulted in immunosuppressive macrophage polarization. In summary, TIMP1/CHI3L1 might be perceived as a diagnostic marker and an immunotherapy target for gliomas.

神经胶质瘤是高度异质性的脑肿瘤，对治疗有抵抗力。神经胶质瘤的分子特征在肿瘤预后和治疗中发挥着重要作用。此外，具有间充质表型的神经胶质瘤患者表现出强烈的免疫抑制和对治疗的复杂抵抗。因此，对神经胶质瘤中基因/蛋白质共表达网络和中心基因的研究有望确定有效的治疗策略。因此，在这项研究中，我们的目标是。使用平均连锁层次聚类，描述了 13 个模块和 224 个中心基因。从最有意义的模块中选出的前十个中心基因（CLIC1、 EMP3、TIMP1、 CCDC109B、CASP4、 MSN、 ANXA2P2、CHI3L1、TAGLN2、S100A11）与不良预后相关。字符串分析、免疫共沉淀和免疫荧光显示 TIMP1 和 CHI3L1 之间存在显着相关性。此外，我们发现，在体内和体外，TIMP1 通过 CHI3L1 过表达以及 NF-κB 激活促进神经胶质瘤发生。 TIMP1表达与肿瘤免疫浸润和免疫检查点相关基因表达相关。此外，TIMP1导致免疫抑制性巨噬细胞极化。总之，TIMP1/CHI3L1 可能被视为神经胶质瘤的诊断标记物和免疫治疗靶点。