Department of Neurosurgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, China.
School of Clinical Medicine, Sanquan College of Xinxiang Medical University, Xinxiang, Henan, China.
Cancer Biol Ther. 2024 Dec 31;25(1):2425134. doi: 10.1080/15384047.2024.2425134. Epub 2024 Nov 18.
DSN1 has been previously found to be positively correlated with various cancers. However, the effect of DSN1 or its methylation on the prognosis, molecular characteristics, and immune cell infiltration of low-grade glioma (LGG) has not yet been studied. We obtained 1046 LGG samples from the The Cancer Genome Atlas, The Chinese Glioma Genome Atlas (CGGA) microarray, and CGGA RNA-Seq databases. Bioinformatic methods (gene set enrichment analysis (GSEA), chi-square test, multivariate), and laboratory validation were used to investigate DSN1 in LGG. The expression levels of DSN1 mRNA and protein in LGG were substantially higher than those in normal brain tissue, and their expression was negatively regulated by methylation. The survival time of patients with low expression of DSN1 and cg12601032 hypermethylation was considerably prolonged. DSN1 was a risk factor, and of good diagnostic and prognostic value for LGG. Importantly, the expression of DSN1 is related to many types of tumor-infiltrating immune cells and has a positive correlation with PDL1. DSN1 promoted the activation of multiple cancer-related pathways, such as the cell cycle. Additionally, knockdown of DSN1 substantially inhibited the proliferation and invasion of LGG cells. To the best of our knowledge, this study is the first comprehensive analysis of the mechanism of DSN1 leading to poor prognosis of LGG, which provides a new perspective for revealing the pathogenesis of LGG. DSN1 or its methylation has diagnostic value for the prognosis of glioma, and may become a new biological target of anti-tumor immunotherapy.
DSN1 先前被发现与多种癌症呈正相关。然而,DSN1 或其甲基化对低级别胶质瘤 (LGG) 的预后、分子特征和免疫细胞浸润的影响尚未得到研究。我们从 The Cancer Genome Atlas、The Chinese Glioma Genome Atlas (CGGA) 微阵列和 CGGA RNA-Seq 数据库中获得了 1046 个 LGG 样本。我们使用生物信息学方法(基因集富集分析 (GSEA)、卡方检验、多变量)和实验室验证来研究 LGG 中的 DSN1。DSN1 mRNA 和蛋白质在 LGG 中的表达水平明显高于正常脑组织,并且其表达受到甲基化的负调控。DSN1 低表达和 cg12601032 高甲基化的患者的生存时间明显延长。DSN1 是 LGG 的危险因素,具有良好的诊断和预后价值。重要的是,DSN1 的表达与多种肿瘤浸润免疫细胞有关,并且与 PDL1 呈正相关。DSN1 促进了多个与癌症相关的途径的激活,如细胞周期。此外,DSN1 的敲低显著抑制了 LGG 细胞的增殖和侵袭。据我们所知,这项研究是首次全面分析 DSN1 导致 LGG 预后不良的机制,为揭示 LGG 的发病机制提供了新的视角。DSN1 或其甲基化对胶质瘤的预后具有诊断价值,可能成为抗肿瘤免疫治疗的新的生物靶点。