Fan Huanhuan, Zhang Shuxin, Yuan Yunbo, Chen Siliang, Li Wenhao, Wang Zhihao, Xiang Yufan, Li Junhong, Ma Xiaohong, Liu Yanhui
Psychiatric Laboratory and Mental Health Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
Front Neurol. 2023 Mar 10;14:1104738. doi: 10.3389/fneur.2023.1104738. eCollection 2023.
Diffuse gliomas possess a kind of malignant brain tumor with high mortality. Glutamine represents the most abundant and versatile amino acid in the body. Glutamine not only plays an important role in cell metabolism but also involves in cell survival and malignancies progression. Recent studies indicate that glutamine could also affect the metabolism of immune cells in the tumor microenvironment (TME).
The transcriptome data and clinicopathological information of patients with glioma were acquired from TCGA, CGGA, and West China Hospital (WCH). The glutamine metabolism-related genes (GMRGs) were retrieved from the Molecular Signature Database. Consensus clustering analysis was used to discover expression patterns of GMRGs, and glutamine metabolism risk scores (GMRSs) were established to model tumor aggressiveness-related GMRG expression signature. ESTIMATE and CIBERSORTx were applied to depict the TME immune landscape. The tumor immunological phenotype analysis and TIDE were utilized for predicting the therapeutic response of immunotherapy.
A total of 106 GMRGs were retrieved. Two distinct clusters were established by consensus clustering analysis, which showed a close association with the IDH mutational status of gliomas. In both IDH-mutant and IDH-wildtype gliomas, cluster 2 had significantly shorter overall survival compared with cluster 1, and the differentially expressed genes between the two clusters enriched in pathways related to malignant transformation as well as immunity. TME analysis of the two IDH subtypes revealed not only significantly different immune cell infiltrations and immune phenotypes between the GMRG expression clusters but also different predicted responses to immunotherapy. After the screening, a total of 10 GMRGs were selected to build the GMRS. Survival analysis demonstrated the independent prognostic role of GMRS. Prognostic nomograms were established to predict 1-, 2-, and 3-year survival rates in the four cohorts.
Different subtypes of glutamine metabolism could affect the aggressiveness and TME immune features of diffuse glioma, despite their IDH mutational status. The expression signature of GMRGs could not only predict the outcome of patients with glioma but also be combined into an accurate prognostic nomogram.
弥漫性胶质瘤是一种死亡率很高的恶性脑肿瘤。谷氨酰胺是人体内含量最丰富、功能最多样的氨基酸。谷氨酰胺不仅在细胞代谢中起重要作用，还参与细胞存活和恶性肿瘤进展。最近的研究表明，谷氨酰胺还可能影响肿瘤微环境（TME）中免疫细胞的代谢。
从TCGA、CGGA和华西医院（WCH）获取胶质瘤患者的转录组数据和临床病理信息。从分子特征数据库中检索谷氨酰胺代谢相关基因（GMRG）。采用一致性聚类分析来发现GMRG的表达模式，并建立谷氨酰胺代谢风险评分（GMRS）以模拟与肿瘤侵袭性相关的GMRG表达特征。应用ESTIMATE和CIBERSORTx来描绘TME免疫格局。利用肿瘤免疫表型分析和TIDE来预测免疫治疗的疗效。
共检索到106个GMRG。通过一致性聚类分析建立了两个不同的聚类，它们与胶质瘤的异柠檬酸脱氢酶（IDH）突变状态密切相关。在IDH突变型和IDH野生型胶质瘤中，聚类2的总生存期均显著短于聚类1，且两个聚类之间的差异表达基因富集于与恶性转化以及免疫相关的通路。对两种IDH亚型的TME分析不仅揭示了GMRG表达聚类之间免疫细胞浸润和免疫表型的显著差异，还揭示了对免疫治疗的不同预测反应。经过筛选，共选择了10个GMRG来构建GMRS。生存分析证明了GMRS的独立预后作用。建立了预后列线图以预测四个队列中1年, 2年和3年生存率。
尽管弥漫性胶质瘤存在IDH突变状态，但不同亚型的谷氨酰胺代谢可能影响其侵袭性和TME免疫特征。GMRG的表达特征不仅可以预测胶质瘤患者的预后，还可以整合到一个准确的预后列线图中。
