通过生物信息学分析和实验验证CD63作为抑郁症免疫浸润相关的关键生物标志物。

IF 4.9 2区医学 Q1 CLINICAL NEUROLOGY

Journal of affective disorders Pub Date : 2025-06-18 DOI:10.1016/j.jad.2025.119724

Mengyu Liu , Duohao Wang , Yun Sun , Dandan Xu , Yujia Cao , Xinyang Qi , Junjun Sun

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引用次数: 0

摘要

背景：重度抑郁症（MDD）表现出多因素的发病机制，但目前的诊断仍然依赖于临床医生评定的症状量表和现象学访谈，缺乏有效的生物标志物。方法：分析来自基因表达综合数据库（Gene Expression Omnibus database）的人类血液数据集，以鉴定MDD患者与健康对照组（CON）之间的差异表达基因（DEGs）。通过Cytoscape和机器学习算法集成的基因拓扑分析确定关键生物标志物。使用CIBERSORT评估免疫浸润谱。通过多数据库分析构建了蛋白质-蛋白质相互作用（PPI）网络和与候选基因相关的竞争内源RNA （ceRNA）网络，并使用外部数据集进行了验证。最后，通过qPCR和Western blot对候选基因在MDD患者、小鼠模型和细胞中进行验证。结果：利用PPI网络和机器学习算法，CD63被确定为一种潜在的生物标志物。CIBERSORT分析揭示了MDD和CON之间的免疫浸润差异，CD63与免疫检查点HLA-DMB/HLA-DOB相互作用。通过对GSE182194/GSE217811的多数据库分析和验证，hsa-mir-1224-5p与三个长链非编码rna （LINC00630、AP000766.1、LINC02487）形成了cd63相关的ceRNA网络。在MDD患者和抑郁模型小鼠中进行实验验证，SH-SY5Y细胞证实CD63失调。局限性：需要更大的MDD队列来验证研究结果的普遍性；还需要进一步探索MDD患者脑区中CD63的表达。结论：我们的研究结果表明CD63在MDD中作为诊断生物标志物和治疗靶点的双重作用，通过免疫相互作用和ceRNA调节机制介导。CD63可能作为抑郁症的生物标志物，为抑郁症的诊断和治疗提供新的靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

CD63 as a critical biomarker associated with immune infiltration in depression through bioinformatics analysis and experimental validation

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CD63 as a critical biomarker associated with immune infiltration in depression through bioinformatics analysis and experimental validation

Background

Major depressive disorder (MDD) exhibits a multifactorial etiopathogenesis, yet current diagnosis still relies on clinician-rated symptom scales and phenomenological interviews, lacking validated biomarkers.

Methods

We analyzed human blood datasets from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) between MDD patients and healthy controls (CON). Key biomarkers were determined through integrated gene topological analysis in Cytoscape and machine learning algorithms. Immune infiltration profiles were assessed using CIBERSORT. Protein-protein interaction (PPI) networks and competing endogenous RNA (ceRNA) networks associated with candidate genes were constructed via multi-database analysis and validated using external datasets. Finally, candidate gene was validated via qPCR and Western blot in MDD patients, mice models, and cells.

Results

CD63 was identified as a potential biomarker using PPI network and machine learning algorithms. CIBERSORT analysis revealed immune infiltration differences between MDD and CON, with CD63 interacting with immune checkpoints HLA-DMB/HLA-DOB. Through multi-database analysis and validation in GSE182194/GSE217811, hsa-mir-1224-5p and three long non-coding RNAs (LINC00630, AP000766.1, LINC02487) formed CD63-associated ceRNA networks. Experimental validation in MDD patients and depression model mice, and SH-SY5Y cells confirmed CD63 dysregulation.

Limitations

A larger MDD cohort is required to validate the findings' generalizability; further exploration of CD63 expression across brain regions in MDD patients is also needed.

Conclusion

Our findings suggest CD63's dual role as a diagnostic biomarker and therapeutic target in MDD, mediated through immune interaction and ceRNA regulatory mechanisms. CD63 may serve as a biomarker in depression and provide a new target for the diagnosis and therapy of depression.

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来源期刊

Journal of affective disorders 医学-精神病学

CiteScore

10.90

自引率

6.10%

发文量

1319

审稿时长

9.3 weeks

期刊介绍： The Journal of Affective Disorders publishes papers concerned with affective disorders in the widest sense: depression, mania, mood spectrum, emotions and personality, anxiety and stress. It is interdisciplinary and aims to bring together different approaches for a diverse readership. Top quality papers will be accepted dealing with any aspect of affective disorders, including neuroimaging, cognitive neurosciences, genetics, molecular biology, experimental and clinical neurosciences, pharmacology, neuroimmunoendocrinology, intervention and treatment trials.