通过生物信息学分析研究重度抑郁症线粒体和衰老相关基因的生物标志物。

IF 3.2 3区 医学 Q2 PSYCHIATRY
Frontiers in Psychiatry Pub Date : 2025-09-24 eCollection Date: 2025-01-01 DOI:10.3389/fpsyt.2025.1653998
Zhiyuan Chen, Xiaoxiao Tang, Chao Gu, Shaohong Zou
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引用次数: 0

摘要

背景:重度抑郁症(MDD)是一种常见的精神疾病,其发病机制与线粒体功能障碍和细胞衰老有关。本研究旨在利用生物信息学技术鉴定MDD中与线粒体相关基因(MRGs)和衰老相关基因(ARGs)相关的生物标志物。方法:本研究利用GSE201332和GSE52790的数据,包括1136个mrg和866个arg。最初,候选基因通过交叉MRGs、ARGs和从GSE201332的差异表达分析中得到的差异表达基因(DEGs)来选择。通过LASSO回归分析确定候选基因的生物标志物。然后用ROC曲线评估生物标志物,并构建人工神经网络(ANN)模型。随后,进行功能富集、免疫相关分析、药物预测和分子对接。最后,利用逆转录-定量聚合酶链反应(RT-qPCR)验证生物标志物的表达。结果:从4041个DEGs、1136个MRGs和866个ARGs的交叉点中鉴定出7个候选基因,通过LASSO回归分析,SLC25A5、ALDH2、CPT1C和imt被确定为MDD的潜在生物标志物。GSE201332和GSE52790的ROC曲线分析显示,这些生物标志物能够有效区分MDD和对照样品,AUC值均超过0.7。人工神经网络模型进一步证实了这些生物标志物的诊断潜力。基因集富集分析(GSEA)显示SLC25A5、CPT1C和IMMT在细胞蛋白复合物组装和染色质组织相关途径中显著富集。免疫浸润分析显示SLC25A5、ALDH2和IMMT与18种免疫细胞类型中的大多数呈显著正相关。分子对接预测发现ALDH2和SLC25A5是特异性药物的潜在靶点,其中硝化甘油与ALDH2的结合亲和力最佳(-6.4 kcal/mol)。RT-qPCR验证显示,与对照组相比,MDD患者SLC25A5和imt的表达显著降低,CPT1C的表达显著升高(p < 0.05),与生物信息学预测一致。结论:本研究发现SLC25A5、ALDH2、CPT1C和imt是与MDD相关的生物标志物,为MDD的分子机制提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Investigating biomarkers of mitochondrial and aging-related genes in major depressive disorder through bioinformatics analysis.

Background: Major depressive disorder (MDD) is a prevalent mental health condition in which mitochondrial dysfunction and cellular senescence contribute to its pathogenesis. This study aims to identify biomarkers related to mitochondria-associated genes (MRGs) and aging-related genes (ARGs) in MDD using bioinformatics.

Methods: This study utilized data from GSE201332 and GSE52790, including 1,136 MRGs and 866 ARGs. Initially, candidate genes were selected by intersecting MRGs, ARGs, and differentially expressed genes (DEGs) derived from differential expression analysis in GSE201332. Biomarkers were identified through LASSO regression analysis of the candidate genes. The biomarkers were then evaluated using ROC curves, and artificial neural network (ANN) models were constructed. Subsequently, functional enrichment, immune-related analyses, drug predictions, and molecular docking were performed. Finally, the expression of biomarkers was validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR).

Results: Seven candidate genes were identified from the intersection of 4,041 DEGs, 1,136 MRGs, and 866 ARGs, with SLC25A5, ALDH2, CPT1C, and IMMT identified as potential biomarkers for MDD through LASSO regression analysis. ROC curve analysis in both GSE201332 and GSE52790 showed that these biomarkers effectively distinguished between MDD and control samples, with AUC values exceeding 0.7. ANN models further confirmed the diagnostic potential of these biomarkers. Gene set enrichment analysis (GSEA) revealed significant enrichment of SLC25A5, CPT1C, and IMMT in pathways related to cellular protein complex assembly and chromatin organization. Immune infiltration analysis demonstrated significant positive correlations between SLC25A5, ALDH2, and IMMT and most of the 18 immune cell types. Molecular docking predictions identified ALDH2 and SLC25A5 as potential targets for specific drugs, with NITROGLYCERIN showing the best binding affinity to ALDH2 (-6.4 kcal/mol). RT-qPCR validation showed significantly lower expression of SLC25A5 and IMMT, and higher expression of CPT1C, in patients with MDD compared to controls (p < 0.05), consistent with bioinformatics predictions.

Conclusion: This study identified SLC25A5, ALDH2, CPT1C, and IMMT as biomarkers associated with MDD, offering insights into its molecular mechanisms.

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来源期刊
Frontiers in Psychiatry
Frontiers in Psychiatry Medicine-Psychiatry and Mental Health
CiteScore
6.20
自引率
8.50%
发文量
2813
审稿时长
14 weeks
期刊介绍: Frontiers in Psychiatry publishes rigorously peer-reviewed research across a wide spectrum of translational, basic and clinical research. Field Chief Editor Stefan Borgwardt at the University of Basel is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide. The journal''s mission is to use translational approaches to improve therapeutic options for mental illness and consequently to improve patient treatment outcomes.
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