Department of Cellular and Molecular Biology, North Tehran Branch, Islamic Azad University, Tehran, Iran.
Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Azadi Sq., Hezar Jerib Ave, P.O. Code, Isfahan, 81746-73441, Iran.
Neurol Sci. 2023 Aug;44(8):2753-2761. doi: 10.1007/s10072-023-06738-4. Epub 2023 Mar 28.
Diagnosis of Parkinson's disease (PD) is associated with a vast number of challenges. This study aimed to assess the overlap of PD patients' transcriptomes in the substantia nigra (SN) with peripheral blood mononuclear cells (PBMCs) to discover potential biomarkers for diagnosis.
GEO data were used to select genes with significant changes in expression level in the SN region and eligible studies. Also, transcriptome data related to blood of PD patients with other neurodegenerative diseases (ND) was considered. Differential expression genes between PD and control were evaluated in the SN and blood, and RT-qPCR was applied to validate the findings.
At the expression level, no significant similarity in long non-coding RNA was found between the patients' SN and blood. While in silico results revealed 16 common mRNAs in SN and blood with significant expression levels. Among all overexpressed mRNAs, HSPA1A/B expression level had the highest expression difference between control and PD samples. Moreover, DGKH had the highest score of down-regulated genes in both blood and SN. The NOTCH pathway had the highest score pathway among up-regulated pathways, and the expression levels of NOTCH2, H4C8, and H2BC21 associated with this pathway had the most ability to separate the control and PD populations. Furthermore, RT-qPCR results revealed that HSPA1A/B, NOTCH2, and H4C8 were overexpressed in PD PBMCs, while DGKH expression levels were lower compared to controls.
Our findings indicate that expression levels of HSPA1A/B, DGKH, and NOTCH2 could be applied as candidate biomarkers to diagnose PD patients in the SN region and PBMCs.
帕金森病（PD）的诊断存在诸多挑战。本研究旨在评估黑质（SN）中 PD 患者转录组与外周血单核细胞（PBMC）之间的重叠，以发现潜在的诊断生物标志物。
使用 GEO 数据选择 SN 区域和符合条件的研究中表达水平有显著变化的基因。同时，还考虑了与 PD 患者血液中其他神经退行性疾病（ND）相关的转录组数据。在 SN 和血液中评估 PD 与对照之间差异表达基因，并应用 RT-qPCR 对结果进行验证。
在表达水平上，患者 SN 和血液之间的长非编码 RNA 没有明显的相似性。而在 SN 和血液中存在 16 个共同的差异表达 mRNAs。在所有过表达的 mRNAs 中，HSPA1A/B 在对照和 PD 样本之间的表达差异最大。此外，DGKH 在血液和 SN 中均为下调基因中得分最高的基因。NOTCH 通路是上调通路中得分最高的通路，与该通路相关的 NOTCH2、H4C8 和 H2BC21 的表达水平具有将对照和 PD 人群区分开来的最大能力。此外，RT-qPCR 结果表明，HSPA1A/B、NOTCH2 和 H4C8 在 PD PBMC 中过表达，而 DGKH 的表达水平低于对照。
我们的研究结果表明，HSPA1A/B、DGKH 和 NOTCH2 的表达水平可作为候选生物标志物，用于诊断 SN 区域和 PBMC 中的 PD 患者。
