Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, PR China.
Department of Neuro-Oncology, Neurosurgery Center, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, PR China.
Int Immunopharmacol. 2020 Jun;83:106400. doi: 10.1016/j.intimp.2020.106400. Epub 2020 Mar 16.
Docking protein 3 has been implicated in immune response, including interferon-β production in macrophage and plasma cell differentiation. And its importance in lung adenocarcinoma has been reported. However, studies about its role in gliomas are rare. In this study, we explored the clinical and prognostic characteristics of DOK3 expression in 921 glioma samples. Kaplan-Meier survival analysis and Cox regression analysis verified the independent unfavorable prognostic value and high prognostic accuracy of DOK3 expression for overall survival. Functional analysis with Database for Annotation, Visualization and Integrated Discovery (DAVID) and Gene Set Enrichment Analysis (GSEA) implied the involvement of DOK3 in immune related responses. Immune cell infiltration analysis with online tools, CIBERSORT and EPIC, showed that samples with higher DOK3 expression were infiltrated with much more macrophages. DOK3 was also found to be strongly positively correlated with marker genes of tumor-associated macrophages and M2 macrophages, not M1. Results of immunohistochemical staining also demonstrated that samples with higher DOK3 expression level were infiltrated with more microglia/macrophages and immunosuppressive M2 macrophages. In summary, our results demonstrated the correlation between high DOK3 expression level and malignant progression of gliomas, and the possible involvement of DOK3 in immunosuppressive responses in gliomas.
对接蛋白 3 已被牵涉到免疫反应中,包括巨噬细胞中干扰素-β的产生和浆细胞分化。并且它在肺腺癌中的重要性已被报道。然而,关于其在神经胶质瘤中的作用的研究却很少。在这项研究中,我们探索了 921 例神经胶质瘤样本中 DOK3 表达的临床和预后特征。Kaplan-Meier 生存分析和 Cox 回归分析验证了 DOK3 表达对总生存期的独立不良预后价值和高预后准确性。通过数据库注释、可视化和综合发现 (DAVID) 和基因集富集分析 (GSEA) 的功能分析表明 DOK3 参与了免疫相关反应。使用在线工具 CIBERSORT 和 EPIC 进行免疫细胞浸润分析表明,DOK3 表达较高的样本浸润了更多的巨噬细胞。DOK3 还与肿瘤相关巨噬细胞和 M2 巨噬细胞的标志物基因呈强正相关,而不是 M1。免疫组化染色的结果也表明,DOK3 表达水平较高的样本浸润了更多的小胶质细胞/巨噬细胞和免疫抑制性 M2 巨噬细胞。总之,我们的结果表明 DOK3 高表达水平与神经胶质瘤的恶性进展之间存在相关性,并且 DOK3 可能参与了神经胶质瘤中的免疫抑制反应。
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