| 张宏,展淑琴.脂质代谢关键基因在帕金森病中的挖掘及其功能分析[J].安徽医药,2024,28(12):2377-2380. |
| 脂质代谢关键基因在帕金森病中的挖掘及其功能分析 |
| Data mining and functional analysis of key lipid metabolism genes in Parkinson's disease |
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| DOI：10.3969/j.issn.1009-6469.2024.12.009 |
| 中文关键词: 帕金森病 生物信息学 关键基因 脂质代谢 NOTUM |
| 英文关键词: Parkinson's disease Bioinformatics Key gene Lipid metabolism NOTUM |
| 基金项目:国家自然科学基金资助项目( 81070999) |
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| 中文摘要: |
| 目的挖掘与帕金森病( PD)发生关系密切的脂质代谢相关关键基因，并对其相关功能进行分析。方法于 2023年 6—12月通过基因表达综合数据库( GEO)和 R语言包分析差异基因( DEGs)。利用 “clusterProfiler”R包进行疾病本体( DO)、基因本体( GO)和京都基因和基因组数据库( KEGG)富集分析，在 Metascape软件中进行数据分析。使用网络分析工具，计算基因网络中的节点度和中心性，筛选出关键基因。使用公共数据库 GEPIA2进行基因差异分析，使用 “survival”软件包通过 Cumula-tive-Survival生存曲线评估整体生存率，使用 Timer、CIBERSORT、EPIC和 xCell等工具分析 CD8+T细胞免疫浸润水平，使用 Tim-er2.0评估与 PD测序结果相关的 CD8+T细胞丰度确定关键基因的初步功能。结果差异基因 DO分析发现差异基因主要富集在性发育疾病、性腺疾病中； KEGG基因富集分析提示，这些差异基因主要集中在 Wnt信号通路。 GO分析提示，显著变化的差异基因主要为经典 Wnt信号通路、 Wnt信号通路和 Wnt调控的细胞间信号。识别 PD HUB关键基因为 NOTUM。对其功能分析发现 NOTUM基因在人类肿瘤组织中亦存在基因突变，突变最常见的形式是过度扩增，过度扩增后可减少 CD8+T细胞的浸润，导致预后差。结论基于生信分析发现脂质代谢关键基因 ——NOTUM在 PD中高表达， PD与免疫功能异常有关。 |
| 英文摘要: |
| Objective To excavate key genes related to lipid metabolism that are closely associated with the development of Parkin-son's disease (PD) and to analyze their related functions.Methods Differential genes (DEGs) were analyzed between June 2023 andDecember 2023 using the Gene Expression Omnibus (GEO) database and the R package. Disease Ontology (DO), Gene Ontology (GO),and Kyoto Gene and Genome Database (KEGG) enrichment analyses were performed using the "clusterProfiler" R package, and the da-ta were analyzed in Metascape software. Using a network analysis tool, the node degree and centrality in the gene network were calculat-ed and key genes were screened. Differential gene analysis was performed using the public database GEPIA2, and overall survival wasassessed by Cumulative-Survival survival curves using the "survival" software package, and analyzed using tools such as Timer, CIBERSORT, EPIC, and xCell. The level of immune infiltration of CD8+ T cells was analyzed using tools such as Timer, CIBERSORT, EPIC, and xCell, and the abundance of CD8+ T cells was assessed using Timer2.0 to correlate with the PD sequencing results to deter-mine the initial function of key genes.Results Differential gene DO analysis revealed that the differential genes were mainly enrichedin sex development diseases and gonadal diseases; KEGG gene enrichment analysis suggested that these differential genes were mainlyconcentrated in Wnt signaling pathway. GO analysis suggested that the significantly altered differential genes were mainly in classicalWnt signaling pathway, Wnt signaling pathway and Wnt-regulated intercellular signaling. The key gene of PD HUB was identified asNOTUM, and its functional analysis revealed that NOTUM gene was also mutated in human tumor tissues, and the most common formof mutation was over-expansion, which could reduce the infiltration of CD8+ T-cells and lead to poor prognosis.Conclusion Bioinfor-matics-based analysis revealed that 1 key gene for lipid metabolism, NOTUM, was highly expressed in PD, and PD was found to be as-sociated with abnormal immune function. |
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