Liu Chen, Qiao Huilian, Li Hongqi, Hu Xiaolong, Yan Maohui, Fu Zhiguang, Zhang Hengheng, Wang Yingjie, Du Nan
Medical School of Chinese People's Liberation Army (PLA), Beijing, China.
Department of Oncology, the Fifth Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.
Front Immunol. 2025 Apr 9;16:1512186. doi: 10.3389/fimmu.2025.1512186. eCollection 2025.
Glioma is a major cause of mortality among central nervous system tumors, with a generally poor prognosis. The lysyl oxidase (LOX) family, a group of copper-dependent amine oxidases, has been implicated in the progression of various cancers, but its specific role in glioma and its relationship with immune infiltration remains insufficiently explored. This study aims to investigate the LOX family's expression, prognostic significance, and immune infiltration dynamics in glioma to identify potential therapeutic targets.
A comprehensive analysis was conducted using public databases to assess gene expression, mutation frequency, and immune infiltration patterns related to the LOX family in glioma. The results were validated through survival analysis and immunohistochemistry. Functional assays, including EdU, Transwell, and flow cytometry, were used to evaluate glioma cell proliferation, migration, invasion, and apoptosis. Co-culture experiments with immune cells, ELISA, and a glioma transplantation model were employed to study the immune-modulatory effects of the LOX family. Gene and protein expression levels were further analyzed using qRT-PCR and Western blotting.
The LOX family was significantly upregulated in low-grade gliomas and strongly associated with poor clinical outcomes. Although mutation frequencies were low, the LOX family contributed to glioma progression through pathways involving metastasis, hypoxia response, angiogenesis, and immune cell infiltration. LOX expression correlated with increased infiltration of macrophages and eosinophils and decreased presence of Treg and CD8+ T cells. Knockdown of LOX genes impaired glioma cell functions, induced apoptosis, and altered immune cell behavior by reducing M2 macrophage polarization and enhancing CD8+ T cell activity.
The LOX family is overexpressed in glioma and is associated with poor prognosis and altered immune infiltration patterns. These findings highlight the LOX family as a promising prognostic marker and therapeutic target, particularly for enhancing the effectiveness of immunotherapy in glioma treatment.
神经胶质瘤是中枢神经系统肿瘤中导致死亡的主要原因，总体预后通常较差。赖氨酰氧化酶（LOX）家族是一组铜依赖性胺氧化酶，已被证明与多种癌症的进展有关，但其在神经胶质瘤中的具体作用及其与免疫浸润的关系仍未得到充分研究。本研究旨在调查LOX家族在神经胶质瘤中的表达、预后意义及免疫浸润动态变化，以确定潜在的治疗靶点。
利用公共数据库进行综合分析，以评估神经胶质瘤中与LOX家族相关的基因表达、突变频率和免疫浸润模式。通过生存分析和免疫组织化学对结果进行验证。采用包括EdU、Transwell和流式细胞术在内的功能测定法评估神经胶质瘤细胞的增殖、迁移、侵袭和凋亡。通过与免疫细胞共培养实验、酶联免疫吸附测定（ELISA）和神经胶质瘤移植模型研究LOX家族的免疫调节作用。使用实时定量聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法进一步分析基因和蛋白质表达水平。
LOX家族在低级别神经胶质瘤中显著上调，且与不良临床结果密切相关。尽管突变频率较低，但LOX家族通过涉及转移、缺氧反应、血管生成和免疫细胞浸润的途径促进神经胶质瘤进展。LOX表达与巨噬细胞和嗜酸性粒细胞浸润增加以及调节性T细胞（Treg）和CD8+T细胞数量减少相关。敲低LOX基因会损害神经胶质瘤细胞功能，诱导细胞凋亡，并通过减少M2巨噬细胞极化和增强CD8+T细胞活性改变免疫细胞行为。
LOX家族在神经胶质瘤中过表达，与不良预后和免疫浸润模式改变相关。这些发现突出了LOX家族作为一种有前景的预后标志物和治疗靶点的地位，特别是在增强神经胶质瘤免疫治疗效果方面。
