Tang Yanliang, Zhang Xiaoli, Tang Xiaofei, Yuan Ye, Wang Wenwen
Department of Neurology, Fuyang Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang, China.
Front Oncol. 2025 Jul 16;15:1613423. doi: 10.3389/fonc.2025.1613423. eCollection 2025.
Lactic acid is a by-product of energy metabolism and a signaling molecule that influences tumor progression by regulating immune cell function, angiogenesis, and epigenetic modifications.
This study analyzed data from the TCGA database on gliomas to systematically elucidate the expression patterns, prognostic value, and functional regulatory networks of lactylation-related genes.
In this study, 17 lactylation-related prognostic genes were identified through the analysis of TCGA-GBM data. Using non- negative matrix factorization (NMF), two GBM subtypes based on lactylation- related genes (LRGs), termed GBM1 and GBM2, were identified. Survival analysis revealed that the overall survival (OS) of the GBM1 group was significantly lower than that of GBM2 group. Furthermore, notable differences were observed in the expression of key GBM-associated molecular markers between the two subtypes. Tumor microenvironment (TME) analysis demonstrated distinct immune landscapes and genomic characteristics between GBM1 and GBM2. The GBM1 group exhibited higher immune cell infiltration and immune function scores compared to GBM2. Drug sensitivity analysis further revealed differences in response to chemotherapy and targeted therapies between the two subtypes. In vitro data demonstrated that LCP1 knockdown suppressed cell proliferation and invasion, and promoted apoptosis in glioma cells.
In conclusion, our study systematically uncovers the significant role of LRGs in GBM molecular subtyping, prognosis evaluation, and therapeutic guidance. These findings offer new insights and potential strategies for the personalized treatment of GBM.
乳酸是能量代谢的副产物,也是一种信号分子,通过调节免疫细胞功能、血管生成和表观遗传修饰来影响肿瘤进展。
本研究分析了来自TCGA数据库的胶质瘤数据,以系统阐明乳酸化相关基因的表达模式、预后价值和功能调控网络。
在本研究中,通过对TCGA-GBM数据的分析,鉴定出17个乳酸化相关的预后基因。使用非负矩阵分解(NMF),基于乳酸化相关基因(LRGs)鉴定出两种GBM亚型,分别称为GBM1和GBM2。生存分析显示,GBM1组的总生存期(OS)显著低于GBM2组。此外,在两种亚型之间观察到关键GBM相关分子标志物的表达存在显著差异。肿瘤微环境(TME)分析表明GBM1和GBM2之间存在不同的免疫格局和基因组特征。与GBM2相比,GBM1组表现出更高的免疫细胞浸润和免疫功能评分。药物敏感性分析进一步揭示了两种亚型对化疗和靶向治疗反应的差异。体外数据表明,LCP1基因敲低抑制了胶质瘤细胞的增殖和侵袭,并促进了其凋亡。
总之,我们的研究系统地揭示了LRGs在GBM分子分型、预后评估和治疗指导中的重要作用。这些发现为GBM的个性化治疗提供了新的见解和潜在策略。