Identification of Mitophagy-Related Genes and Analysis of Immune Infiltration in Atherosclerosis.

IF 4.1 2区 医学 Q2 IMMUNOLOGY
Journal of Inflammation Research Pub Date : 2025-10-03 eCollection Date: 2025-01-01 DOI:10.2147/JIR.S544597
Jiaqi Zhang, Xiting Wang, Xiahuan Chen, Meilin Liu
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引用次数: 0

Abstract

Background: Atherosclerosis is a chronic inflammatory disease involving mitophagy and immune dysregulation. Currently, there is no integrated diagnostic model for autophagy immune genes in mitochondria. This study aimed to identify potential diagnostic markers through integrated bioinformatics and experimental validation.

Methods: Two atherosclerosis-related datasets (GSE43292 and GSE100927) were analyzed to identify differentially expressed mitophagy-related genes (MRGs), followed by enrichment analysis. Key genes were screened using LASSO, SVM-RFE, and random forest algorithms. A diagnostic nomogram was constructed and validated by ROC analysis. Immune infiltration was evaluated using CIBERSORT and ssGSEA. GSEA, GSVA, and unsupervised clustering were applied to explore biological pathways and molecular subtypes. qPCR validation was performed in ox-LDL-treated RAW264.7 and THP-1 cells.

Results: Thirteen upregulated and six downregulated MRGs were identified. Five hub genes (MNDA, CD163L1, NEXN, TC2N, SLC22A3) demonstrated strong diagnostic performance (AUC > 0.85) and were closely associated with immune cell infiltration; two molecular subtypes with distinct immune profiles were identified; qPCR validation confirmed the differential expression of these genes under inflammatory stimulation.

Conclusion: MNDA, CD163L1, NEXN, TC2N, and SLC22A3 may serve as diagnostic biomarkers for atherosclerosis. This five-gene model can stratify patient risk and guide personalized anti-inflammatory/autophagic therapy.

动脉粥样硬化中线粒体自噬相关基因的鉴定及免疫浸润分析。
背景:动脉粥样硬化是一种涉及线粒体自噬和免疫失调的慢性炎症性疾病。目前,线粒体自噬免疫基因还没有一个完整的诊断模型。本研究旨在通过综合生物信息学和实验验证来鉴定潜在的诊断标志物。方法:分析两个动脉粥样硬化相关数据集(GSE43292和GSE100927),鉴定差异表达的有丝分裂相关基因(MRGs),然后进行富集分析。使用LASSO、SVM-RFE和随机森林算法筛选关键基因。建立诊断模式图,并进行ROC分析验证。采用CIBERSORT和ssGSEA评价免疫浸润。应用GSEA, GSVA和无监督聚类来探索生物学途径和分子亚型。在ox- ldl处理的RAW264.7和THP-1细胞中进行qPCR验证。结果:鉴定出13个上调的mrg和6个下调的mrg。5个中心基因(MNDA、CD163L1、NEXN、TC2N、SLC22A3)表现出较强的诊断效能(AUC > 0.85),与免疫细胞浸润密切相关;鉴定出两种具有不同免疫谱的分子亚型;qPCR验证证实了这些基因在炎症刺激下的差异表达。结论:MNDA、CD163L1、NEXN、TC2N和SLC22A3可作为动脉粥样硬化的诊断性生物标志物。这种五基因模型可以对患者风险进行分层,并指导个性化的抗炎/自噬治疗。
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 Inflammation Research
Journal of Inflammation Research Immunology and Microbiology-Immunology
CiteScore
6.10
自引率
2.20%
发文量
658
审稿时长
16 weeks
期刊介绍: An international, peer-reviewed, open access, online journal that welcomes laboratory and clinical findings on the molecular basis, cell biology and pharmacology of inflammation.
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