Department of Radiotherapy, the Second Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Pathology, Stanford University School of Medicine, Stanford, CA, United States.
Front Immunol. 2022 Jun 23;13:917014. doi: 10.3389/fimmu.2022.917014. eCollection 2022.
Among the most common types of brain tumor, gliomas are the most aggressive and have the poorest prognosis. Dolichyl-diphosphooligosaccharide protein glycosyltransferase non-catalytic subunit (DDOST) encodes a component of the oligosaccharide transferase complex and is related to the N-glycosylation of proteins. The role of DDOST in gliomas, however, is not yet known. First, we performed a pan cancer analysis of DDOST in the TCGA cohort. The expression of DDOST was compared between glioma and normal brain tissues in the GEO and Chinese Glioma Genome Atlas (CGGA) databases. In order to explore the role of DDOST in glioma, we analyze the impact of DDOST on the prognosis of glioma patients, with the CGGA 325 dataset as a test set and the CGGA 693 dataset as a validation set. Immunohistochemistry was performed on tissue microarrays to examine whether DDOST has an impact on glioma patient survival. Next, using single-cell sequencing analysis, GSEA, immune infiltration analysis, and mutation analysis, we explored how DDOST affected the glioma tumor microenvironment. Finally, we evaluated the clinical significance of DDOST for glioma treatment by constructing nomograms and decision curve analysis (DCA) curves. We found that DDOST was overexpressed in patients with high grade, IDH wild type, 1p19q non-codel and MGMT un-methylated, which was associated with poor prognosis. Patients with high levels of DDOST, regardless of their clinical characteristics, had a worse prognosis. Immunohistochemical analysis confirmed the results of the above bioinformatics analysis. Mechanistic analysis revealed that DDOST was closely associated with the glioma microenvironment and negatively related to tumor-infiltrating B cells and CD4+ T cells and positively related to CAFs and tumor-associated macrophages. In conclusion, these findings suggested that DDOST mediated the immunosuppressive microenvironment of gliomas and could be an important biomarker in diagnosing and treating gliomas.
在最常见的脑肿瘤类型中，神经胶质瘤的侵袭性最强，预后最差。Dolichyl-diphosphooligosaccharide protein glycosyltransferase non-catalytic subunit (DDOST) 编码寡糖转移酶复合物的一个组成部分，与蛋白质的 N-糖基化有关。然而，DDOST 在神经胶质瘤中的作用尚不清楚。首先，我们在 TCGA 队列中对 DDOST 进行了泛癌症分析。在 GEO 和中国神经胶质瘤基因组图谱 (CGGA) 数据库中比较了神经胶质瘤和正常脑组织中 DDOST 的表达。为了探讨 DDOST 在神经胶质瘤中的作用，我们分析了 DDOST 对神经胶质瘤患者预后的影响，以 CGGA 325 数据集作为测试集，CGGA 693 数据集作为验证集。通过组织微阵列进行免疫组织化学检测，以研究 DDOST 是否对神经胶质瘤患者的生存产生影响。接下来，我们通过单细胞测序分析、GSEA、免疫浸润分析和突变分析，探讨了 DDOST 如何影响神经胶质瘤肿瘤微环境。最后，我们通过构建列线图和决策曲线分析 (DCA) 曲线评估了 DDOST 对神经胶质瘤治疗的临床意义。我们发现，在高级别、IDH 野生型、1p19q 非共缺失和 MGMT 未甲基化的患者中，DDOST 表达上调，与预后不良相关。无论患者的临床特征如何，高水平的 DDOST 患者预后更差。免疫组织化学分析证实了上述生物信息学分析的结果。机制分析表明，DDOST 与神经胶质瘤微环境密切相关，与肿瘤浸润性 B 细胞和 CD4+T 细胞呈负相关，与 CAFs 和肿瘤相关巨噬细胞呈正相关。总之，这些发现表明 DDOST 介导了神经胶质瘤的免疫抑制微环境，可能是诊断和治疗神经胶质瘤的重要生物标志物。
