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Abstract：
BACKGROUND: The WD40 repeat (WDR) domain provides scaffolds for numerous protein-protein interactions in multiple biological processes. WDR domain 76 (WDR76) has complex functionality owing to its diversified interactions; however, its mechanism in LGG has not yet been reported.
METHODS: Transcriptomic data from public databases were multifariously analyzed to explore the role of WDR76 in LGG pathology and tumor immunity. Laboratory experiments were conducted to confirm these results.
RESULTS: The results first confirmed that high expression of WDR76 in LGG was not only positively associated with clinical and molecular features of malignant LGG, but also served as an independent prognostic factor that predicted shorter survival in patients with LGG. Furthermore, high expression of WDR76 resulted in the upregulation of oncogenes, such as PRC1 and NUSAP1, and the activation of oncogenic mechanisms, such as the cell cycle and Notch signaling pathway. Finally, WDR76 was shown to be involved in LGG tumor immunity by promoting the infiltration of immune cells, such as M2 macrophages, and the expression of immune checkpoints, such as PDCD1 (encoding PD-1).
CONCLUSIONS: This study shows for the first time the diagnostic and prognostic value of WDR76 in LGG and provides a novel personalized biomarker for future targeted therapy and immunotherapy. Thus, WDR76 may significantly improve the prognosis of patients with LGG.
METHODS: Transcriptomic data from public databases were multifariously analyzed to explore the role of WDR76 in LGG pathology and tumor immunity. Laboratory experiments were conducted to confirm these results.
RESULTS: The results first confirmed that high expression of WDR76 in LGG was not only positively associated with clinical and molecular features of malignant LGG, but also served as an independent prognostic factor that predicted shorter survival in patients with LGG. Furthermore, high expression of WDR76 resulted in the upregulation of oncogenes, such as PRC1 and NUSAP1, and the activation of oncogenic mechanisms, such as the cell cycle and Notch signaling pathway. Finally, WDR76 was shown to be involved in LGG tumor immunity by promoting the infiltration of immune cells, such as M2 macrophages, and the expression of immune checkpoints, such as PDCD1 (encoding PD-1).
CONCLUSIONS: This study shows for the first time the diagnostic and prognostic value of WDR76 in LGG and provides a novel personalized biomarker for future targeted therapy and immunotherapy. Thus, WDR76 may significantly improve the prognosis of patients with LGG.
摘要：
背景：WD40重复（WDR）结构域为多种生物过程中的许多蛋白质-蛋白质相互作用提供了支架。WDR域76(WDR76)由于其多样化的交互而具有复杂的功能；然而，其在LGG中的作用机制尚未见报道。
方法：对来自公共数据库的转录组数据进行多重分析，以探讨WDR76在LGG病理学和肿瘤免疫中的作用。进行实验室实验以证实这些结果。
结果：结果首先证实，WDR76在LGG中的高表达不仅与恶性LGG的临床和分子特征呈正相关，但也可作为预测LGG患者生存期较短的独立预后因素。此外，WDR76的高表达导致癌基因的上调，如PRC1和NUSAP1，以及致癌机制的激活，如细胞周期和Notch信号通路。最后,WDR76被证明通过促进免疫细胞的浸润参与LGG肿瘤的免疫，如M2巨噬细胞，以及免疫检查点的表达，例如PDCD1(编码PD-1)。
结论：这项研究首次显示了WDR76在LGG中的诊断和预后价值，并为未来的靶向治疗和免疫疗法提供了一种新的个性化生物标志物。因此，WDR76可明显改善LGG患者的预后。
方法：对来自公共数据库的转录组数据进行多重分析，以探讨WDR76在LGG病理学和肿瘤免疫中的作用。进行实验室实验以证实这些结果。
结果：结果首先证实，WDR76在LGG中的高表达不仅与恶性LGG的临床和分子特征呈正相关，但也可作为预测LGG患者生存期较短的独立预后因素。此外，WDR76的高表达导致癌基因的上调，如PRC1和NUSAP1，以及致癌机制的激活，如细胞周期和Notch信号通路。最后,WDR76被证明通过促进免疫细胞的浸润参与LGG肿瘤的免疫，如M2巨噬细胞，以及免疫检查点的表达，例如PDCD1(编码PD-1)。
结论：这项研究首次显示了WDR76在LGG中的诊断和预后价值，并为未来的靶向治疗和免疫疗法提供了一种新的个性化生物标志物。因此，WDR76可明显改善LGG患者的预后。
