Maimaiti Aierpati, Wang Xixian, Hao Yujun, Jiang Lei, Shi Xin, Pei Yinan, Feng Zhaohai, Kasimu Maimaitijiang
Department of Functional Neurosurgery, Neurosurgery Centre, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, Xinjiang, China.
J Mol Neurosci. 2021 Aug;71(8):1622-1635. doi: 10.1007/s12031-021-01817-7. Epub 2021 Mar 13.
Glioma is one of the most common neurological malignancies worldwide. Delta-like ligand 3 (DLL3), an inhibitory ligand-driven activation of the Notch pathway, has been shown to be significantly associated with overall survival in patients with glioma. Therefore, the purpose of this study was to determine whether DLL3 as a biomarker in glioma is associated with patients' clinicopathological features and prognosis. We identified differences in transcriptome and promoter methylation in the Chinese Glioma Genome Atlas (CGGA) in patients with malignant glioma with shorter (less than 1 year) and longer (greater than 3 years) survival time. Further analysis of The Cancer Genome Atlas (TCGA) revealed that four genes (DLL3, TSPAN15, RTN1, PAK7) are highly associated with patient prognosis and play an indispensable role in evolution. We chose the expression level of DLL3 in glioma patients for our study. Patients were divided into groups with low and high expression of DLL3 according to the cutoff values obtained, and Kaplan-Meier and Cox analysis were used to examine the correlation between DLL3 gene expression and patient survival. We then performed a gene set enrichment analysis (GSEA) to identify significantly enriched signaling pathways. Our results confirmed that the overall survival of patients with low DLL3 expression was significantly shorter than that of patients with high DLL3 expression. GSEA showed that the signaling pathways of the immune process and immune response, among others, were enhanced with the DLL3 low-expression phenotype. Collectively, our findings signify that DLL3 is a potent prognostic factor for glioma, which can provide a viable approach for glioma prognostic assessment and valuable insights for anti-tumor immune-targeted therapies.
胶质瘤是全球最常见的神经恶性肿瘤之一。Delta样配体3（DLL3）是一种由抑制性配体驱动的Notch通路激活剂，已被证明与胶质瘤患者的总生存期显著相关。因此，本研究的目的是确定DLL3作为胶质瘤的生物标志物是否与患者的临床病理特征和预后相关。我们在中国胶质瘤基因组图谱（CGGA）中鉴定了生存时间较短（少于1年）和较长（大于3年）的恶性胶质瘤患者的转录组和启动子甲基化差异。对癌症基因组图谱（TCGA）的进一步分析显示，四个基因（DLL3、TSPAN15、RTN1、PAK7）与患者预后高度相关，并在肿瘤进展中起不可或缺的作用。我们选择胶质瘤患者中DLL3的表达水平进行研究。根据获得的临界值将患者分为DLL3低表达组和高表达组，并使用Kaplan-Meier和Cox分析来检验DLL3基因表达与患者生存之间的相关性。然后，我们进行了基因集富集分析（GSEA）以确定显著富集的信号通路。我们的结果证实，DLL3低表达患者的总生存期明显短于DLL3高表达患者。GSEA显示，免疫过程和免疫反应等信号通路在DLL3低表达表型中增强。总的来说，我们的研究结果表明DLL3是胶质瘤的一个有力预后因素，可为胶质瘤预后评估提供可行的方法，并为抗肿瘤免疫靶向治疗提供有价值的见解。
