Liao Zhangjun, Wu Shuyi, Shi Zhenyi, Chen Donghui, Chen Jinrui, Zhang Hua
Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, School of Medical Technology, Guangdong Medical University, Dongguan 523808, China.
Int J Mol Sci. 2025 Jun 27;26(13):6205. doi: 10.3390/ijms26136205.
High-grade gliomas (HGGs, WHO grades 3-4) are highly aggressive, with a poor prognosis and treatment resistance. Immune evasion may contribute to their progression, but the role of cytotoxic T-lymphocyte immune evasion (CTLE) is not well-validated. This study analyzed the transcriptomic data of 525 patients from TCGA-GBM-HG_U133A. Two molecular subtypes were identified based on 182 CTLE-associated genes, with 238 differentially expressed genes between them. A prognostic model was developed, identifying BST2 and DIRAS3 as key risk factors, and validated in multiple cohorts. The subtypes had distinct immune profiles, with Cluster 2 showing higher immune infiltration but a poorer prognosis. The model had a good predictive performance. High-risk patients had upregulated BST2 and DIRAS3, linked to immunosuppression and shorter survival. Knockdown experiments confirmed their roles in GBM cell migration and invasion. Mechanistically, they promote immune evasion. BST2 and DIRAS3 could be therapeutic targets for HGG immunotherapy.
高级别胶质瘤（HGGs，世界卫生组织3-4级）具有高度侵袭性，预后不良且具有治疗抗性。免疫逃逸可能促进其进展，但细胞毒性T淋巴细胞免疫逃逸（CTLE）的作用尚未得到充分验证。本研究分析了来自TCGA-GBM-HG_U133A的525例患者的转录组数据。基于182个CTLE相关基因鉴定出两种分子亚型，它们之间有238个差异表达基因。建立了一个预后模型，确定BST2和DIRAS3为关键风险因素，并在多个队列中进行了验证。这些亚型具有不同的免疫特征，第2组显示出更高的免疫浸润但预后较差。该模型具有良好的预测性能。高危患者的BST2和DIRAS3上调，与免疫抑制和较短生存期相关。敲低实验证实了它们在胶质母细胞瘤细胞迁移和侵袭中的作用。从机制上讲，它们促进免疫逃逸。BST2和DIRAS3可能是HGG免疫治疗的治疗靶点。
