Tianjin Neurological Institute, Key Laboratory of Post Neuro-Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin 300052, China; Department of Neurosurgery, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin 300052, China.
Department of Neurosurgery, Tianjin Medical University General Hospital, 154 Anshan Road, Tianjin 300052, China.
Biochim Biophys Acta Mol Basis Dis. 2024 Mar;1870(3):167041. doi: 10.1016/j.bbadis.2024.167041. Epub 2024 Jan 28.
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，对治疗有抗性。神经胶质瘤的分子特征在肿瘤预后和治疗中起着重要作用。此外，具有间充质表型的神经胶质瘤患者表现出强大的免疫抑制作用和对治疗的复杂抗性。因此，研究神经胶质瘤中的基因/蛋白质共表达网络和枢纽基因有望确定有效的治疗策略。因此，在这项研究中，我们旨在......使用平均链接层次聚类，描述了 13 个模块和 224 个枢纽基因。从最有意义的模块中选择的前 10 个枢纽基因（CLIC1、EMP3、TIMP1、CCDC109B、CASP4、MSN、ANXA2P2、CHI3L1、TAGLN2、S100A11）与预后不良相关。String 分析、共免疫沉淀和免疫荧光显示 TIMP1 与 CHI3L1 之间存在显著相关性。此外，我们发现，无论是在体内还是体外，TIMP1 都通过 CHI3L1 的过表达以及 NF-κB 的激活来促进神经胶质瘤的发生。TIMP1 的表达与肿瘤免疫浸润和免疫检查点相关基因的表达相关。此外，TIMP1 导致了免疫抑制性巨噬细胞的极化。总之，TIMP1/CHI3L1 可被视为神经胶质瘤的诊断标志物和免疫治疗靶点。
