{"title":"慢性鼻炎伴鼻息肉线粒体相关特征的机器学习和生物信息学综合分析","authors":"","doi":"10.1016/j.waojou.2024.100964","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent inflammatory disorder affecting the upper respiratory tract. Recent studies have indicated an association between CRSwNP and mitochondrial metabolic disorder characterized by impaired metabolic pathways; however, the precise mechanisms remain unclear. This study aims to investigate the mitochondrial-related signature in individuals diagnosed with CRSwNP.</div></div><div><h3>Methods</h3><div>Through the integration of differentially expressed genes (DEGs) with the mitochondrial gene set, differentially expressed mitochondrial-related genes (DEMRGs) were identified. Subsequently, the hub DEMRGs were selected using 4 integrated machine learning algorithms. Immune and mitochondrial characteristics were estimated based on CIBERSORT and ssGSEA algorithms. Bioinformatic findings were confirmed through RT-qPCR, immunohistochemistry, and ELISA for nasal tissues, as well as Western blotting analysis for human nasal epithelial cells (hNECs). The relationship between hub DEMRGs and disease severity was assessed using Spearman correlation analysis.</div></div><div><h3>Results</h3><div>A total of 24 DEMRGs were screened, most of which exhibited lower expression levels in CRSwNP samples. Five hub DEMRGs (<em>ALDH1L1</em>, <em>BCKDHB</em>, <em>CBR3</em>, <em>HMGCS2</em>, and <em>OXR1</em>) were consistently downregulated in both the discovery and validation cohorts. The hub genes showed a high diagnostic performance and were positively correlated with the infiltration of M2 macrophages and resting mast cells. Experimental results confirmed that the 5 genes were downregulated at both the mRNA and protein levels within nasal polyp tissues. Finally, a significant and inverse relationship was identified between the expression levels of these genes and both the Lund-Mackay and Lund-Kennedy scores.</div></div><div><h3>Conclusion</h3><div>Our findings systematically unraveled 5 hub markers correlated with mitochondrial metabolism and immune cell infiltration in CRSwNP, suggesting their potential to be based to design diagnostic and therapeutic strategies for the disease.</div></div>","PeriodicalId":54295,"journal":{"name":"World Allergy Organization Journal","volume":null,"pages":null},"PeriodicalIF":3.9000,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1939455124000954/pdfft?md5=0aa4daa07b7c3b9fd971ce2e75c9690d&pid=1-s2.0-S1939455124000954-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Integrated machine learning and bioinformatic analysis of mitochondrial-related signature in chronic rhinosinusitis with nasal polyps\",\"authors\":\"\",\"doi\":\"10.1016/j.waojou.2024.100964\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent inflammatory disorder affecting the upper respiratory tract. Recent studies have indicated an association between CRSwNP and mitochondrial metabolic disorder characterized by impaired metabolic pathways; however, the precise mechanisms remain unclear. This study aims to investigate the mitochondrial-related signature in individuals diagnosed with CRSwNP.</div></div><div><h3>Methods</h3><div>Through the integration of differentially expressed genes (DEGs) with the mitochondrial gene set, differentially expressed mitochondrial-related genes (DEMRGs) were identified. Subsequently, the hub DEMRGs were selected using 4 integrated machine learning algorithms. Immune and mitochondrial characteristics were estimated based on CIBERSORT and ssGSEA algorithms. Bioinformatic findings were confirmed through RT-qPCR, immunohistochemistry, and ELISA for nasal tissues, as well as Western blotting analysis for human nasal epithelial cells (hNECs). The relationship between hub DEMRGs and disease severity was assessed using Spearman correlation analysis.</div></div><div><h3>Results</h3><div>A total of 24 DEMRGs were screened, most of which exhibited lower expression levels in CRSwNP samples. Five hub DEMRGs (<em>ALDH1L1</em>, <em>BCKDHB</em>, <em>CBR3</em>, <em>HMGCS2</em>, and <em>OXR1</em>) were consistently downregulated in both the discovery and validation cohorts. The hub genes showed a high diagnostic performance and were positively correlated with the infiltration of M2 macrophages and resting mast cells. Experimental results confirmed that the 5 genes were downregulated at both the mRNA and protein levels within nasal polyp tissues. Finally, a significant and inverse relationship was identified between the expression levels of these genes and both the Lund-Mackay and Lund-Kennedy scores.</div></div><div><h3>Conclusion</h3><div>Our findings systematically unraveled 5 hub markers correlated with mitochondrial metabolism and immune cell infiltration in CRSwNP, suggesting their potential to be based to design diagnostic and therapeutic strategies for the disease.</div></div>\",\"PeriodicalId\":54295,\"journal\":{\"name\":\"World Allergy Organization Journal\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-09-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S1939455124000954/pdfft?md5=0aa4daa07b7c3b9fd971ce2e75c9690d&pid=1-s2.0-S1939455124000954-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"World Allergy Organization Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1939455124000954\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ALLERGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"World Allergy Organization Journal","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1939455124000954","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ALLERGY","Score":null,"Total":0}
Integrated machine learning and bioinformatic analysis of mitochondrial-related signature in chronic rhinosinusitis with nasal polyps
Background
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent inflammatory disorder affecting the upper respiratory tract. Recent studies have indicated an association between CRSwNP and mitochondrial metabolic disorder characterized by impaired metabolic pathways; however, the precise mechanisms remain unclear. This study aims to investigate the mitochondrial-related signature in individuals diagnosed with CRSwNP.
Methods
Through the integration of differentially expressed genes (DEGs) with the mitochondrial gene set, differentially expressed mitochondrial-related genes (DEMRGs) were identified. Subsequently, the hub DEMRGs were selected using 4 integrated machine learning algorithms. Immune and mitochondrial characteristics were estimated based on CIBERSORT and ssGSEA algorithms. Bioinformatic findings were confirmed through RT-qPCR, immunohistochemistry, and ELISA for nasal tissues, as well as Western blotting analysis for human nasal epithelial cells (hNECs). The relationship between hub DEMRGs and disease severity was assessed using Spearman correlation analysis.
Results
A total of 24 DEMRGs were screened, most of which exhibited lower expression levels in CRSwNP samples. Five hub DEMRGs (ALDH1L1, BCKDHB, CBR3, HMGCS2, and OXR1) were consistently downregulated in both the discovery and validation cohorts. The hub genes showed a high diagnostic performance and were positively correlated with the infiltration of M2 macrophages and resting mast cells. Experimental results confirmed that the 5 genes were downregulated at both the mRNA and protein levels within nasal polyp tissues. Finally, a significant and inverse relationship was identified between the expression levels of these genes and both the Lund-Mackay and Lund-Kennedy scores.
Conclusion
Our findings systematically unraveled 5 hub markers correlated with mitochondrial metabolism and immune cell infiltration in CRSwNP, suggesting their potential to be based to design diagnostic and therapeutic strategies for the disease.
期刊介绍：
The official pubication of the World Allergy Organization, the World Allergy Organization Journal (WAOjournal) publishes original mechanistic, translational, and clinical research on the topics of allergy, asthma, anaphylaxis, and clincial immunology, as well as reviews, guidelines, and position papers that contribute to the improvement of patient care. WAOjournal publishes research on the growth of allergy prevalence within the scope of single countries, country comparisons, and practical global issues and regulations, or threats to the allergy specialty. The Journal invites the submissions of all authors interested in publishing on current global problems in allergy, asthma, anaphylaxis, and immunology. Of particular interest are the immunological consequences of climate change and the subsequent systematic transformations in food habits and their consequences for the allergy/immunology discipline.
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