鉴定儿童过敏性哮喘中的线粒体相关生物标志物。

Identification of mitochondria-related biomarkers in childhood allergic asthma.

机构信息

Department of Pediatrics, The Second People's Hospital of Hefei, Hefei, Anhui, China.

出版信息

BMC Med Genomics. 2024 May 23;17(1):141. doi: 10.1186/s12920-024-01901-y.

DOI:10.1186/s12920-024-01901-y

PMID:38783263

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11112767/

Abstract

BACKGROUND

The mechanism of mitochondria-related genes (MRGs) in childhood allergic asthma (CAS) was unclear. The aim of this study was to find new biomarkers related to MRGs in CAS.

METHODS

This research utilized two CAS-related datasets (GSE40888 and GSE40732) and extracted 40 MRGs from the MitoCarta3.0 Database. Initially, differential expression analysis was performed on CAS and control samples in the GSE40888 dataset to obtain the differentially expressed genes (DEGs). Differentially expressed MRGs (DE-MRGs) were obtained by overlapping the DEGs and MRGs. Protein protein interactions (PPI) network of DE-MRGs was created and the top 10 genes in the degree ranking of Maximal Clique Centrality (MCC) algorithm were defined as feature genes. Hub genes were obtained from the intersection genes from the Least absolute shrinkage and selection operator (LASSO) and EXtreme Gradient Boosting (XGBoost) algorithms. Additionally, the expression validation was conducted, functional enrichment analysis, immune infiltration analysis were finished, and transcription factors (TFs)-miRNA-mRNA regulatory network was constructed.

RESULTS

A total of 1505 DEGs were obtained from the GSE40888, and 44 DE-MRGs were obtained. A PPI network based on these 44 DE-MRGs was created and revealed strong interactions between ADCK5 and MFN1, BNIP3 and NBR1. Four hub genes (NDUFAF7, MTIF3, MRPS26, and NDUFAF1) were obtained by taking the intersection of genes from the LASSO and XGBoost algorithms based on 10 signature genes which obtained from PPI. In addition, hub genes-based alignment diagram showed good diagnostic performance. The results of Gene Set Enrichment Analysis (GSEA) suggested that hub genes were closely related to mismatch repair. The B cells naive cells were significantly expressed between CAS and control groups, and MTIF3 was most strongly negatively correlated with B cells naive. In addition, the expression of MTIF3 and MRPS26 may have influenced the inflammatory response in CAS patients by affecting mitochondria-related functions. The quantitative real-time polymerase chain reaction (qRT‒PCR) results showed that four hub genes were all down-regulated in the CAS samples.

CONCLUSION

NDUFAF7, MTIF3, MRPS26, and NDUFAF1 were identified as an MRGs-related biomarkers in CAS, which provides some reference for further research on CAS.

摘要

背景

线粒体相关基因（MRGs）在儿童过敏性哮喘（CAS）中的作用机制尚不清楚。本研究旨在寻找与 CAS 相关的新的 MRGs 相关生物标志物。

方法

本研究利用两个 CAS 相关数据集（GSE40888 和 GSE40732），并从 MitoCarta3.0 数据库中提取 40 个 MRGs。首先，对 GSE40888 数据集的 CAS 和对照样本进行差异表达分析，以获得差异表达基因（DEGs）。通过重叠 DEGs 和 MRGs，获得差异表达的 MRGs（DE-MRGs）。创建 DE-MRGs 的蛋白质蛋白质相互作用（PPI）网络，并定义最大团中心度（MCC）算法中度数排名前 10 的基因作为特征基因。通过最小绝对收缩和选择算子（LASSO）和极端梯度增强（XGBoost）算法的交集基因获得枢纽基因。此外，进行了表达验证，完成了功能富集分析、免疫浸润分析，并构建了转录因子（TFs）-miRNA-mRNA 调控网络。

结果

从 GSE40888 中获得了 1505 个 DEGs，获得了 44 个 DE-MRGs。基于这 44 个 DE-MRGs 创建了一个 PPI 网络，揭示了 ADCK5 和 MFN1、BNIP3 和 NBR1 之间的强烈相互作用。通过基于 PPI 的 10 个特征基因的 LASSO 和 XGBoost 算法的交集，获得了 4 个枢纽基因（NDUFAF7、MTIF3、MRPS26 和 NDUFAF1）。此外，基于枢纽基因的比对图显示出良好的诊断性能。基因集富集分析（GSEA）的结果表明，枢纽基因与错配修复密切相关。CAS 组和对照组之间 B 细胞幼稚细胞的表达差异显著，MTIF3 与 B 细胞幼稚细胞的相关性最强。此外，MTIF3 和 MRPS26 的表达可能通过影响与线粒体相关的功能影响 CAS 患者的炎症反应。实时定量聚合酶链反应（qRT-PCR）结果表明，CAS 样本中四个枢纽基因均下调。