Mutational profiling of low-grade gliomas identifies prognosis and immunotherapy-related biomarkers and tumour immune microenvironment characteristics

低级别胶质瘤的突变谱分析可识别预后和免疫治疗相关的生物标志物以及肿瘤免疫微环境特征。

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Abstract

Low-grade glioma (LGG) is a heterogeneous tumour with the median survival rate less than 10 years. Therefore, it is urgent to develop efficient immunotherapy strategies of LGG. In this study, we analysed mutation profiles based on the data of 510 LGG patients from the Cancer Genome Atlas (TCGA) database and investigated the prognostic value of mutated genes and evaluate their immune infiltration. Tumor Immune Dysfunction and Exclusion (TIDE) algorithm was used to indicate the characteristics of gliomas that respond to immune checkpoint blockade (ICB) therapy. Univariate and multivariate cox regression analysis was performed to identify indicators to construct the nomogram model. 485 (95.47%) of 508 LGG samples showed gene mutation, and 9 mutated genes were significantly related to overall survival (OS), among which 6 mutated genes were significantly correlated with OS between mutation and wildtypes. Immune infiltration and immune score analyses revealed that these six mutated genes were significantly associated with tumour immune microenvironment in LGG. The response of LGG with different characteristics to ICB was evaluated by TIDE algorithm. Finally, CIC gene was screened through both univariate and multivariate Cox regression analyses, and the nomogram model was established to determine the potential prognostic value of CIC in LGG. Our study provides comprehensive analysis of mutated genes in LGG, supporting modulation of mutated genes in the management of LGG.

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