Department of Neurology, Peking University Shenzhen Hospital, Shenzhen, China.
Department of Neurology, Shenzhen Second People's Hospital, Shenzhen, China.
Sci Rep. 2023 Aug 29;13(1):14122. doi: 10.1038/s41598-023-41066-9.
This study aimed to identify hub genes and pathological mechanisms related to neuroinflammation in Sporadic Creutzfeldt-Jakob disease (SCJD) based on comprehensive bioinformatics. SCJD and normal samples were collected from GSE160208. Weighted gene co-expression network analysis (WGCNA) and Limma R package were used to obtain key genes, which were used for enrichment and immune cell infiltration analyses. Protein-protein interaction (PPI) network, cytoHubba, and machine learning were used to screen the central genes of SCJD. The chemicals related to hub genes were predicted and explored by molecular docking. 88 candidate genes were screened. Enrichment analysis showed they were mainly related to bacterial and viral infection and immune cell activation. Immune cell infiltration analysis suggested that immune cell activation and altered activity of the immune system are involved in the progression of SCJD. After identifying hub genes, KIT and SPP1 had higher diagnostic efficacy for SCJD (AUC > 0.9), so they were identified as central genes. The molecular docking results showed hub genes both docked well with Tretinoin. KIT, SPP1, and Tretinoin are essential in developing neuroinflammation in SCJD and may provide new ideas for diagnosing and treating SCJD.
本研究旨在基于综合生物信息学方法，鉴定与散发性克雅氏病（SCJD）神经炎症相关的枢纽基因和病理机制。从 GSE160208 中收集了 SCJD 和正常样本。使用加权基因共表达网络分析（WGCNA）和 Limma R 包获得关键基因，用于富集和免疫细胞浸润分析。蛋白质-蛋白质相互作用（PPI）网络、cytoHubba 和机器学习用于筛选 SCJD 的中心基因。通过分子对接预测和探索与枢纽基因相关的化学物质。筛选出 88 个候选基因。富集分析表明，它们主要与细菌和病毒感染以及免疫细胞激活有关。免疫细胞浸润分析表明，免疫细胞激活和免疫系统功能改变参与了 SCJD 的进展。确定枢纽基因后，KIT 和 SPP1 对 SCJD 具有更高的诊断效能（AUC>0.9），因此被鉴定为中心基因。分子对接结果表明，枢纽基因与维 A 酸均结合良好。KIT、SPP1 和维 A 酸在 SCJD 中神经炎症的发生发展中至关重要，可能为 SCJD 的诊断和治疗提供新的思路。
