Zhang Xue, Song Shuo, Zhou Defen, Cui Hanwei, Xie Jiangan
School of Life Health Information Science and Engineering, Chongqing University of Posts and Telecommunications, Chongqing, 400065, P. R. China.
Central Laboratory, Shenzhen Samii Medical Center, Shenzhen, 518118, Guangdong, P.R. China.
Sci Rep. 2025 Jul 12;15(1):25210. doi: 10.1038/s41598-025-09646-z.
Low-grade glioma(LGG) is a prevalent primary brain tumor, and type I interferons(IFN-Is) can exert a multifaceted influence on the regulation of the tumor microenvironment during its initiation and progression. To investigate the role of IFN-Is in the progression of LGG, we screened public databases for features based on IFN-alpha(IFN-α) response genes (IRGs), a risk model was constructe and its relationship to tumor immunity and prognosis was evaluated. In addition, the expression and regulation of IRGs in LGG were further studied in vitro biological function experiments and immunohistochemistry of clinical samples. 20 differential genes associated with LGG-IRGs were found, then 6-IRGs-based signature was found by using of univariate COX, LASSO and SVM-RFE. ROC curves also supported the value of signature. CIBERSORT results demonstrated the crucial role played by these key signature genes in immune response. Additionally, aggregation analysis of relevant immune-related genes revealed that cluster 1 exhibited the lowest expression of RIPK2 and SELL. Moreover, GSVA results suggested that diagnostic immune-related genes may regulate LGG by influencing immune cells. We further validated these findings using external datasets and provided additional evidence supporting the predictive value of signature genes associated with IRGs in LGG through immunohistochemical testing on clinical samples and in vitro experiments. These 6 diagnostic IRGs genes can help differentiate and predict the prognosis and immune status of patients with LGG, thereby providing new strategies for precise and personalized immunotherapy.
低级别胶质瘤（LGG）是一种常见的原发性脑肿瘤，I型干扰素（IFN-Is）在其起始和进展过程中可对肿瘤微环境的调节产生多方面影响。为了研究IFN-Is在LGG进展中的作用，我们基于IFN-α反应基因（IRGs）在公共数据库中筛选特征，构建了一个风险模型，并评估其与肿瘤免疫和预后的关系。此外，还通过体外生物学功能实验和临床样本的免疫组织化学进一步研究了LGG中IRGs的表达和调控。发现了20个与LGG-IRGs相关的差异基因，然后通过单变量COX、LASSO和支持向量机递归特征消除（SVM-RFE）找到了基于6个IRGs的特征。ROC曲线也支持该特征的价值。CIBERSORT结果证明了这些关键特征基因在免疫反应中所起的关键作用。此外，相关免疫相关基因的聚集分析表明，簇1表现出最低的RIPK2和SELL表达。而且，基因集变异分析（GSVA）结果表明，诊断性免疫相关基因可能通过影响免疫细胞来调节LGG。我们使用外部数据集进一步验证了这些发现，并通过对临床样本的免疫组织化学检测和体外实验提供了额外证据，支持与IRGs相关的特征基因在LGG中的预测价值。这6个诊断性IRGs基因有助于区分和预测LGG患者的预后和免疫状态，从而为精准和个性化免疫治疗提供新策略。
