School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China.
Department of Neurosurgery, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Front Immunol. 2024 Oct 9;15:1467858. doi: 10.3389/fimmu.2024.1467858. eCollection 2024.
Low-grade gliomas (LGG) represent a heterogeneous and complex group of brain tumors. Despite significant progress in understanding and managing these tumors, there are still many challenges that need to be addressed. Glycosylation, a common post-translational modification of proteins, plays a significant role in tumor transformation. Numerous studies have demonstrated a close relationship between glycosylation modifications and tumor progression. However, the biological function of glycosylation-related genes in LGG remains largely unexplored. Their potential roles within the LGG microenvironment are also not well understood.
We collected RNA-seq data and scRNA-seq data from patients with LGG from TCGA and GEO databases. The glycosylation pathway activity scores of each cluster and each patient were calculated by irGSEA and GSVA algorithms, and the differential genes between the high and low glycosylation pathway activity score groups were identified. Prognostic risk profiles of glycosylation-related genes were constructed using univariate Cox and LASSO regression analyses and validated in the CGGA database.
An 8 genes risk score signature including ASPM, CHI3L1, LILRA4, MSN, OCIAD2, PTGER4, SERPING1 and TNFRSF12A was constructed based on the analysis of glycosylation-related genes. Patients with LGG were divided into high risk and low risk groups according to the median risk score. Significant differences in immunological characteristics, TIDE scores, drug sensitivity, and immunotherapy response were observed between these groups. Additionally, survival analysis of clinical medication information in the TCGA cohort indicated that high risk and low risk groups have different sensitivities to drug therapy. The risk score characteristics can thus guide clinical medication decisions for LGG patients.
Our study established glycosylation-related gene risk score signatures, providing new perspectives and approaches for prognostic prediction and treatment of LGG.
低级别胶质瘤(LGG)代表了一组异质性和复杂性的脑肿瘤。尽管在理解和管理这些肿瘤方面取得了重大进展,但仍有许多挑战需要解决。糖基化是蛋白质的一种常见翻译后修饰,在肿瘤转化中发挥着重要作用。大量研究表明糖基化修饰与肿瘤进展密切相关。然而,糖基化相关基因在 LGG 中的生物学功能仍在很大程度上未被探索。它们在 LGG 微环境中的潜在作用也尚未被很好地理解。
我们从 TCGA 和 GEO 数据库中收集了 LGG 患者的 RNA-seq 数据和 scRNA-seq 数据。通过 irGSEA 和 GSVA 算法计算每个簇和每个患者的糖基化途径活性评分,并鉴定高糖基化途径活性评分组和低糖基化途径活性评分组之间的差异基因。使用单因素 Cox 和 LASSO 回归分析构建糖基化相关基因的预后风险谱,并在 CGGA 数据库中进行验证。
基于糖基化相关基因的分析,构建了一个包括 ASPM、CHI3L1、LILRA4、MSN、OCIAD2、PTGER4、SERPING1 和 TNFRSF12A 在内的 8 个基因风险评分特征。根据中位风险评分将 LGG 患者分为高风险和低风险组。这些组之间观察到免疫特征、TIDE 评分、药物敏感性和免疫治疗反应存在显著差异。此外,TCGA 队列的临床用药信息生存分析表明,高风险组和低风险组对药物治疗的敏感性不同。因此,风险评分特征可以为 LGG 患者的临床用药决策提供指导。
本研究建立了糖基化相关基因风险评分特征,为 LGG 的预后预测和治疗提供了新的视角和方法。