Department of Joint Laboratory for Translational Medicine Research, Liaocheng People's Hospital, Liaocheng, P.R. China.
School of Basic Medicine Sciences, Shandong University, Jinan,P.R. China.
Ann Med. 2024 Dec;56(1):2425064. doi: 10.1080/07853890.2024.2425064. Epub 2024 Nov 18.
This study aimed to identify key genes related to copper metabolism in Parkinson's disease (PD), providing insight into their roles in disease progression.
Using bioinformatic analyses, the study identified hub genes related to copper metabolism in PD patients. Differentially expressed genes (DEGs) were identified using the limma package, and copper-metabolism-related genes (CMRGs) were sourced from the Genecard database. Immune cell-related genes were derived through immune infiltration and Weighted Gene Co-expression Network Analysis (WGCNA). Hub genes were pinpointed by integrating DEGs, CMRGs, and immune cell-related genes. Functional analyses included Receiver Operating Characteristic (ROC) analysis, Ingenuity Pathway Analysis (IPA), and networks for miRNA-mRNA-transcription factor (TF), Competitive Endogenous RNA (ceRNA), and hub gene-drug interactions. Validation was performed in cerebrospinal fluid (CSF) samples from PD patients, while in vitro experiments utilized GBE1- overexpressing SH-SY5Y cells to examine cell proliferation, migration, and viability.
Nine hub genes (HPRT1, GLS, SNCA, MDH1, GBE1, DDC, STXBP1, ACHE, and AGTR1) were identified from 753 CMRGs, 416 DEGs, and 951 immune cell-related genes. ROC analysis showed high predictive accuracy for PD, and principal component analysis (PCA) effectively distinguished PD patients from controls. IPA identified 20 significant pathways, and various networks highlighted miRNA, TF, and drug interactions with the hub genes. Hub gene expression was validated in PD CSF samples. GBE1-overexpressing cells displayed enhanced proliferation, migration, and viability.
The study identified nine copper metabolism-related genes as potential therapeutic targets in PD, highlighting their relevance in PD pathology and possible treatment pathways.
本研究旨在鉴定与帕金森病（PD）中铜代谢相关的关键基因，深入了解它们在疾病进展中的作用。
使用生物信息学分析，本研究鉴定了 PD 患者中与铜代谢相关的枢纽基因。使用 limma 包鉴定差异表达基因（DEGs），并从 Genecard 数据库中获取铜代谢相关基因（CMRGs）。通过免疫细胞浸润和加权基因共表达网络分析（WGCNA）获得免疫细胞相关基因。通过整合 DEGs、CMRGs 和免疫细胞相关基因来确定枢纽基因。功能分析包括接收者操作特征（ROC）分析、Ingenuity 通路分析（IPA）以及 miRNA-mRNA-转录因子（TF）、竞争性内源性 RNA（ceRNA）和枢纽基因-药物相互作用网络。在 PD 患者的脑脊液（CSF）样本中进行验证，同时在体外实验中利用 GBE1 过表达 SH-SY5Y 细胞来检测细胞增殖、迁移和活力。
从 753 个 CMRGs、416 个 DEGs 和 951 个免疫细胞相关基因中鉴定出 9 个枢纽基因（HPRT1、GLS、SNCA、MDH1、GBE1、DDC、STXBP1、ACHE 和 AGTR1）。ROC 分析显示对 PD 具有较高的预测准确性，主成分分析（PCA）有效地将 PD 患者与对照组区分开来。IPA 鉴定出 20 个显著通路，各种网络突出了与枢纽基因的 miRNA、TF 和药物相互作用。在 PD CSF 样本中验证了枢纽基因的表达。GBE1 过表达细胞显示出增强的增殖、迁移和活力。
本研究确定了 9 个与铜代谢相关的基因作为 PD 中的潜在治疗靶点，强调了它们在 PD 病理中的相关性和可能的治疗途径。
