Jiaqi Zhang, Xiting Wang, Xiahuan Chen, Meilin Liu
{"title":"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。","authors":"Jiaqi Zhang, Xiting Wang, Xiahuan Chen, Meilin Liu","doi":"10.2147/JIR.S544597","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"13689-13710"},"PeriodicalIF":4.1000,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503058/pdf/","citationCount":"0","resultStr":"{\"title\":\"Identification of Mitophagy-Related Genes and Analysis of Immune Infiltration in Atherosclerosis.\",\"authors\":\"Jiaqi Zhang, Xiting Wang, Xiahuan Chen, Meilin Liu\",\"doi\":\"10.2147/JIR.S544597\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":16107,\"journal\":{\"name\":\"Journal of Inflammation Research\",\"volume\":\"18 \",\"pages\":\"13689-13710\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2025-10-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503058/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Inflammation Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/JIR.S544597\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Inflammation Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/JIR.S544597","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Identification of Mitophagy-Related Genes and Analysis of Immune Infiltration in Atherosclerosis.
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.
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.