Cheon Jaehwan, Jung Haejin, Kang Byung Yong, Kim Mikyung
Department of Biomedical Science, Korea University College of Medicine, Anam-ro 145, Seongbuk-gu, Seoul, 02841, Republic of Korea.
Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, Hwarang-ro 815, Nowon-gu, Seoul, 01795, Republic of Korea.
Genes Genomics. 2025 Jan;47(1):47-57. doi: 10.1007/s13258-024-01591-x. Epub 2024 Oct 28.
Parkinson's disease (PD) is a progressive neuro-degenerative disorder most common in older adults which is associated with impairments in movement and other body functions. Most PD cases are classified as idiopathic PD (IPD), meaning that the etiology remains unidentified.
To identify key genes and molecular mechanisms to identify biomarkers applicable to IPD.
We applied a bioinformatics approach using a gene expression in whole blood dataset to pinpoint differentially expressed genes (DEGs) and pathways involved in IPD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of DEGs were subsequently performed. A protein-protein interaction (PPI) network was then constructed to select hub genes that may influence IPD. We further investigated the levels of differentially methylated regions (DMRs) and differentially expressed microRNA (DEMs) of whole blood of patients with IPD to validate hub genes. Additionally, we examined the hub gene expression patterns in the substantia nigra (STN) using single-cell RNA sequencing datasets.
In total, we identified 124 DEGs in the blood samples of patients with IPD, with GO and KEGG analyses highlighting their significant enrichment. Analysis of PPI networks revealed three major clusters and hub genes: small nuclear ribonucleoprotein polypeptide E (SNRPE), cytochrome C oxidase subunit 7 C (COX7C), and ribosomal protein S27 (RPS27). DMRs and DEMs analyses revealed hub gene regulation via epigenetic and RNA interference. In particular, SNRPE and RPS27 showed identically regulated gene expression in the STN.
This study suggests that SNRPE, COX7C, and RPS27 in whole-blood samples derived from patients may be useful biomarkers for IPD.
帕金森病(PD)是一种进行性神经退行性疾病,在老年人中最为常见,与运动及其他身体功能障碍有关。大多数帕金森病病例被归类为特发性帕金森病(IPD),这意味着病因仍未明确。
识别关键基因和分子机制,以确定适用于特发性帕金森病的生物标志物。
我们采用生物信息学方法,利用全血数据集的基因表达来确定特发性帕金森病中差异表达基因(DEGs)和相关通路。随后对差异表达基因进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路分析。接着构建蛋白质-蛋白质相互作用(PPI)网络,以选择可能影响特发性帕金森病的枢纽基因。我们进一步研究了特发性帕金森病患者全血中差异甲基化区域(DMRs)和差异表达微小RNA(DEMs)的水平,以验证枢纽基因。此外,我们使用单细胞RNA测序数据集检查了黑质(STN)中的枢纽基因表达模式。
我们总共在特发性帕金森病患者的血液样本中鉴定出124个差异表达基因,GO和KEGG分析突出了它们的显著富集。蛋白质-蛋白质相互作用网络分析揭示了三个主要簇和枢纽基因:小核核糖核蛋白多肽E(SNRPE)、细胞色素C氧化酶亚基7C(COX7C)和核糖体蛋白S27(RPS27)。差异甲基化区域和差异表达微小RNA分析揭示了通过表观遗传和RNA干扰对枢纽基因的调控。特别是,SNRPE和RPS27在黑质中显示出相同的基因表达调控。
本研究表明,来自患者的全血样本中的SNRPE、COX7C和RPS27可能是特发性帕金森病的有用生物标志物。