Lu Chunlin, Ma Huihao, Wang Jie, Sun Fei, Fei Mingyang, Li Ying, Liu Jing, Dong Bin
Department of Neurosurgery, First Affiliated Hospital of Dalian Medical University, Dalian, China.
Department of Stem Cell and Clinical Research, First Affiliated Hospital of Dalian Medical University, Dalian, China.
Front Immunol. 2025 Jan 15;15:1498583. doi: 10.3389/fimmu.2024.1498583. eCollection 2024.
The characteristics and role of NOD-like receptor (NLR) signaling pathway in high-grade gliomas were still unclear. This study aimed to reveal the association of NLR with clinical heterogeneity of glioblastoma (GBM) patients, and to explore the role of NLR pathway hub genes in the occurrence and development of GBM.
Transcriptomic data from 496 GBM patients with complete prognostic information were obtained from the TCGA, GEO, and CGGA databases. Using the NMF clustering algorithm and the expression profiles of NLR genes, these 496 GBM patients were classified into different clinical subtypes. The pathway activity of NLR and the immune micro-environment characteristics were then compared between these subtypes. A novel and accurate NLR expression profile-based prognostic marker for GBM was developed using LASSO and COX regression analysis.
Based on the NLR gene expression profile, GBM patients were accurately divided into two clinical subtypes (C1 and C2) with different clinical outcomes. The two groups of patients showed different immune microenvironment characteristics and metabolic characteristics, which might be the potential reason for the difference in prognosis. Differential expression and enrichment analyzes revealed intrinsic gene signature differences between C1 and C2 subtypes. Based on the differential expression profiles of C1 and C2, prognostic molecular markers related to NLR were developed. The AUC value of the 3-year ROC curve ranged from 0.601 to 0.846, suggesting its potential clinical significance. Single-cell sequencing analysis showed that the NLR gene was mainly active in myeloid cells within GBM. The random forest algorithm identified the crucial role of TRIP6 gene in NLR pathway. Molecular biology experiments confirmed that TRIP6 was abnormally overexpressed in GBM. Knockdown of TRIP6 gene can significantly inhibit the proliferation and migration ability of GBM cells.
The NLR signaling pathway plays a critical role in regulating immune microenvironment and metabolism reprogramming of GBM. TRIP6 is a potential hub gene within the NLR pathway and affects the malignant biological behavior of GBM cells.
NOD样受体（NLR）信号通路在高级别胶质瘤中的特征及作用尚不清楚。本研究旨在揭示NLR与胶质母细胞瘤（GBM）患者临床异质性的关联，并探讨NLR通路枢纽基因在GBM发生发展中的作用。
从TCGA、GEO和CGGA数据库中获取496例具有完整预后信息的GBM患者的转录组数据。利用非负矩阵分解（NMF）聚类算法和NLR基因的表达谱，将这496例GBM患者分为不同的临床亚型。然后比较这些亚型之间NLR的通路活性和免疫微环境特征。使用套索（LASSO）和COX回归分析开发了一种基于NLR表达谱的新型且准确的GBM预后标志物。
基于NLR基因表达谱，GBM患者被准确分为两种临床亚型（C1和C2），其临床结局不同。两组患者表现出不同的免疫微环境特征和代谢特征，这可能是预后差异的潜在原因。差异表达和富集分析揭示了C1和C2亚型之间内在的基因特征差异。基于C1和C2的差异表达谱，开发了与NLR相关的预后分子标志物。3年ROC曲线的AUC值范围为0.601至0.846，表明其潜在的临床意义。单细胞测序分析表明，NLR基因主要在GBM内的髓系细胞中活跃。随机森林算法确定了TRIP6基因在NLR通路中的关键作用。分子生物学实验证实，TRIP6在GBM中异常过表达。敲低TRIP6基因可显著抑制GBM细胞的增殖和迁移能力。
NLR信号通路在调节GBM的免疫微环境和代谢重编程中起关键作用。TRIP6是NLR通路中的一个潜在枢纽基因，影响GBM细胞的恶性生物学行为。
