低级别胶质瘤（LGG）在生物学和转录组水平上具有异质性，其定义和分型仍存在争议。因此，迫切需要特异实用的分子特征来准确诊断、个体化治疗和预后评估。细胞死亡对于维持体内平衡、发展和预防过度增殖性恶性肿瘤至关重要。本研究基于多种程序性细胞死亡（PCD）相关基因和LGG的预后特征，构建模型来探讨LGG细胞转移和侵袭的机制和治疗策略。我们筛选了1161个与PCD相关的基因，并通过一致性聚类分析将512个LGG样本分为C1和C2亚型。我们分析了两种亚型的差异表达基因（DEG）并进行了功能富集分析。使用 ESTIMATE、CIBERSOTR 和 MCPcounter 等 R 包，我们评估了两种亚型的免疫细胞评分。与C1相比，C2亚型预后较差，免疫评分较高，且C2亚型患者与肿瘤进展的相关性更强。 LASSO和COX回归分析筛选出4个特征基因（CLU、FHL3、GIMAP2和HVCN1）。使用不同平台的数据集验证四基因特征，我们发现四基因特征的表达和预后相关性具有高度的稳定性，表现出稳定的预测效果。此外，我们发现CLU、FHL3和GIMAP2的下调显着损害LGG细胞的生长、迁移和侵袭潜力。综上所述，基于PCD相关基因构建的四基因特征为进一步研究LGG的发病机制和临床治疗提供了有价值的信息。© 2024。作者。

Low-grade glioma (LGG) is heterogeneous at biological and transcriptomic levels, and it is still controversial for the definition and typing of LGG. Therefore, there is an urgent need for specific and practical molecular signatures for accurate diagnosis, individualized therapy, and prognostic evaluation of LGG. Cell death is essential for maintaining homeostasis, developing and preventing hyperproliferative malignancies. Based on diverse programmed cell death (PCD) related genes and prognostic characteristics of LGG, this study constructed a model to explore the mechanism and treatment strategies for LGG cell metastasis and invasion. We screened 1161 genes associated with PCD and divided 512 LGG samples into C1 and C2 subtypes by consistent cluster analysis. We analyzed the two subtypes' differentially expressed genes (DEGs) and performed functional enrichment analysis. Using R packages such as ESTIMATE, CIBERSOTR, and MCPcounter, we assessed immune cell scores for both subtypes. Compared with C1, the C2 subtype has a poor prognosis and a higher immune score, and patients in the C2 subtype are more strongly associated with tumor progression. LASSO and COX regression analysis screened four characteristic genes (CLU, FHL3, GIMAP2, and HVCN1). Using data sets from different platforms to validate the four-gene feature, we found that the expression and prognostic correlation of the four-gene feature had a high degree of stability, showing stable predictive effects. Besides, we found downregulation of CLU, FHL3, and GIMAP2 significantly impairs the growth, migration, and invasive potential of LGG cells. Take together, the four-gene feature constructed based on PCD-related genes provides valuable information for further study of the pathogenesis and clinical treatment of LGG.© 2024. The Author(s).