Xu Jiacheng, Guo Yuduo, Ning Weihai, Wang Jun, Chen Yujia, Liu Deshan, Yang Jingjing, Song Yongmei, Zhang Hongwei
Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, China.
Department of Neurosurgery, Xuanwu Hospital, Capital Medical University/China International Neuroscience Institute (China-INI), Beijing, China.
Genes Immun. 2025 Apr 15. doi: 10.1038/s41435-025-00327-5.
In the central nervous system, glioma stands as the predominant primary brain tumor. Heat shock proteins exerted a critical influence on tumor progression and tumor immune microenvironment. However, research on heat shock proteins in glioma remained ambiguous. We analyzed data from the CPTAC, TCGA, and GTEx databases, identifying seven heat shock protein genes critical to glioma prognosis. Subsequently, through Lasso regression, a model based on heat shock protein genes (DNAJC7, DNAJC12, HSPB2, HSP90B1, HSPA5) was constructed. And the risk score showed a positive correlation to the immune score. Further investigation into immune cells revealed that HSPA5 and HSP90B1 were expressed at higher levels in glioma and significantly linked to M2 macrophage infiltration. Considering the limited research on HSP90B1 in glioma, we further revealed that HSP90B1 might have a connection with two crucial signaling pathways within tumors: PI3K/AKT and Wnt/β-catenin. Given that lactate could promote the M2 polarization of macrophages, we further found that HSP90B1 could enhance the transcription of glycolysis-related genes, including LDHA. Overall, our study demonstrated that heat shock protein genes were significantly linked to glioma patient prognosis. Additionally, we observed that HSP90B1 had a significant relationship with M2 macrophage infiltration and potentially regulated LDHA level in glioma.
在中枢神经系统中,胶质瘤是主要的原发性脑肿瘤。热休克蛋白对肿瘤进展和肿瘤免疫微环境具有关键影响。然而,关于胶质瘤中热休克蛋白的研究仍不明确。我们分析了CPTAC、TCGA和GTEx数据库的数据,确定了七个对胶质瘤预后至关重要的热休克蛋白基因。随后,通过套索回归,构建了一个基于热休克蛋白基因(DNAJC7、DNAJC12、HSPB2、HSP90B1、HSPA5)的模型。风险评分与免疫评分呈正相关。对免疫细胞的进一步研究表明,HSPA5和HSP90B1在胶质瘤中表达水平较高,且与M2巨噬细胞浸润显著相关。鉴于对胶质瘤中HSP90B1的研究有限,我们进一步揭示HSP90B1可能与肿瘤内两个关键信号通路:PI3K/AKT和Wnt/β-连环蛋白存在关联。鉴于乳酸可促进巨噬细胞的M2极化,我们进一步发现HSP90B1可增强包括LDHA在内的糖酵解相关基因的转录。总体而言,我们的研究表明热休克蛋白基因与胶质瘤患者预后显著相关。此外,我们观察到HSP90B1与M2巨噬细胞浸润存在显著关系,并可能调节胶质瘤中LDHA水平。