Yang Bo, Gu Min, Hong Chen, Zou Xin-Yuan, Zhang Jia-Qi, Yuan Ye, Qiu Chang-Yu, Lu Mei-Ping, Cheng Lei
Department of Otorhinolaryngology & Clinical Allergy Center, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
International Centre for Allergy Research, Nanjing Medical University, Nanjing, China.
World Allergy Organ J. 2024 Sep 19;17(10):100964. doi: 10.1016/j.waojou.2024.100964. eCollection 2024 Oct.
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.
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.
A total of 24 DEMRGs were screened, most of which exhibited lower expression levels in CRSwNP samples. Five hub DEMRGs (, , , , and ) 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.
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.
伴鼻息肉的慢性鼻-鼻窦炎（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与以代谢途径受损为特征的线粒体代谢紊乱之间存在关联；然而，确切机制仍不清楚。本研究旨在调查诊断为CRSwNP的个体中的线粒体相关特征。
通过将差异表达基因（DEG）与线粒体基因集整合，鉴定出差异表达的线粒体相关基因（DEMRG）。随后，使用4种集成机器学习算法选择核心DEMRG。基于CIBERSORT和ssGSEA算法评估免疫和线粒体特征。通过对鼻组织进行RT-qPCR、免疫组织化学和ELISA，以及对人鼻上皮细胞（hNEC）进行蛋白质印迹分析，证实生物信息学研究结果。使用Spearman相关性分析评估核心DEMRG与疾病严重程度之间的关系。
共筛选出24个DEMRG，其中大多数在CRSwNP样本中表达水平较低。5个核心DEMRG（、、、和）在发现队列和验证队列中均持续下调。这些核心基因显示出较高的诊断性能，并且与M2巨噬细胞和静息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中的mRNA和蛋白质水平均下调。最后，在这些基因的表达水平与Lund-Mackay和Lund-Kennedy评分之间发现了显著的负相关关系。
我们的研究结果系统地揭示了5个与CRSwNP中线粒体代谢和免疫细胞浸润相关的核心标志物，表明它们有可能为该疾病的诊断和治疗策略设计提供依据。
