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

IF 3.9 2区医学 Q2 ALLERGY

World Allergy Organization Journal Pub Date : 2024-09-19 DOI:10.1016/j.waojou.2024.100964

Bo Yang MMed , Min Gu MMed , Chen Hong MMed , Xin-Yuan Zou MMed , Jia-Qi Zhang MBBS , Ye Yuan MBBS , Chang-Yu Qiu MD, MSc , Mei-Ping Lu MD, PhD , Lei Cheng MD, PhD

{"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":"Bo Yang MMed , Min Gu MMed , Chen Hong MMed , Xin-Yuan Zou MMed , Jia-Qi Zhang MBBS , Ye Yuan MBBS , Chang-Yu Qiu MD, MSc , Mei-Ping Lu MD, PhD , Lei Cheng MD, PhD","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":"17 10","pages":"Article 100964"},"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\":\"Bo Yang MMed , Min Gu MMed , Chen Hong MMed , Xin-Yuan Zou MMed , Jia-Qi Zhang MBBS , Ye Yuan MBBS , Chang-Yu Qiu MD, MSc , Mei-Ping Lu MD, PhD , Lei Cheng MD, PhD\",\"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\":\"17 10\",\"pages\":\"Article 100964\"},\"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}

引用次数: 0

摘要

背景慢性鼻炎伴鼻息肉（CRSwNP）是一种影响上呼吸道的常见炎症性疾病。最近的研究表明，CRSwNP 与线粒体代谢紊乱有关，线粒体代谢紊乱的特点是代谢途径受损；然而，确切的机制仍不清楚。方法通过将差异表达基因（DEGs）与线粒体基因组整合，确定了差异表达的线粒体相关基因（DEMRGs）。随后，利用 4 种综合机器学习算法筛选出了中心 DEMRGs。根据 CIBERSORT 和 ssGSEA 算法估计了免疫和线粒体特征。通过鼻组织的 RT-qPCR、免疫组化和 ELISA，以及人鼻上皮细胞（hNECs）的 Western 印迹分析，证实了生物信息学的发现。结果共筛选出 24 个 DEMRGs，其中大多数在 CRSwNP 样本中的表达水平较低。五个中枢 DEMRGs（ALDH1L1、BCKDHB、CBR3、HMGCS2 和 OXR1）在发现队列和验证队列中均持续下调。这些中枢基因显示出很高的诊断性能，并与 M2 巨噬细胞和静止肥大细胞的浸润呈正相关。实验结果证实，这 5 个基因在鼻息肉组织的 mRNA 和蛋白质水平上都出现了下调。结论我们的研究结果系统地揭示了与 CRSwNP 线粒体代谢和免疫细胞浸润相关的 5 个中枢标记，表明它们有可能被用来设计该疾病的诊断和治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

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.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

World Allergy Organization Journal Immunology and Microbiology-Immunology

CiteScore

9.10

自引率

5.90%

发文量

审稿时长

9 weeks

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.