Exploring the hub Genes and Potential Mechanisms of Complement system-related Genes in Parkinson Disease: Based on Transcriptome Sequencing and Mendelian Randomization

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Molecular Neuroscience Pub Date : 2024-10-07 DOI:10.1007/s12031-024-02272-w

Xin Wang, Gaoming Yang, Yali Lai, Yuanyuan Li, Xindong Liu

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Abstract

An accurate diagnosis of Parkinson’s disease (PD) remains challenging and the exact cause of the disease is unclean. The aims are to identify hub genes associated with the complement system in PD and to explore their underlying molecular mechanisms. Initially, differentially expressed genes (DEGs) and key module genes related to PD were mined through differential expression analysis and WGCNA. Then, differentially expressed CSRGs (DE-CSRGs) were obtained by intersecting the DEGs, key module genes and CSRGs. Subsequently, MR analysis was executed to identify genes causally associated with PD. Based on genes with significant MR results, the expression level and diagnostic performance verification were achieved to yield hub genes. Functional enrichment and immune infiltration analyses were accomplished to insight into the pathogenesis of PD. qRT-PCR was employed to evaluate the expression levels of hub genes. After MR analysis and related verification, CD93, CTSS, PRKCD and TLR2 were finally identified as hub genes. Enrichment analysis indicated that the main enriched pathways for hub genes. Immune infiltration analysis found that the hub genes showed significant correlation with a variety of immune cells (such as myeloid-derived suppressor cell and macrophage). In the qRT-PCR results, the expression levels of CTSS, PRKCD and TLR2 were consistent with those we obtained from public databases. Hence, we mined four hub genes associated with complement system in PD which provided novel perspectives for the diagnosis and treatment of PD.

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探索帕金森病中补体系统相关基因的中枢基因和潜在机制：基于转录组测序和孟德尔随机化。

帕金森病（PD）的准确诊断仍然具有挑战性，而且该病的确切病因尚不清楚。本研究旨在确定帕金森病中与补体系统相关的枢纽基因，并探索其潜在的分子机制。首先，通过差异表达分析和WGCNA挖掘与帕金森病相关的差异表达基因（DEGs）和关键模块基因。然后，通过对差异表达基因、关键模块基因和差异表达CSRGs（DE-CSRGs）进行交叉分析，得到差异表达CSRGs（DE-CSRGs）。随后，进行MR分析以确定与帕金森病有因果关系的基因。根据MR结果显著的基因，对其表达水平和诊断性能进行验证，从而得出枢纽基因。通过功能富集和免疫浸润分析，深入了解了帕金森病的发病机制。经过MR分析和相关验证，最终确定CD93、CTSS、PRKCD和TLR2为枢纽基因。富集分析表明，枢纽基因的主要富集通路。免疫浸润分析发现，中心基因与多种免疫细胞（如髓源抑制细胞和巨噬细胞）有显著相关性。在 qRT-PCR 结果中，CTSS、PRKCD 和 TLR2 的表达水平与我们从公共数据库中获得的结果一致。因此，我们挖掘出了与补体系统相关的四个枢纽基因，为诊断和治疗帕金森病提供了新的视角。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Molecular Neuroscience 医学-神经科学

CiteScore

6.60

自引率

3.20%

发文量

142

审稿时长

1 months

期刊介绍： The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.