鉴定和分析过敏性鼻炎相关的脂质代谢基因。

Identification and analysis of lipid metabolism-related genes in allergic rhinitis.

机构信息

Department of Otolaryngology, Changzheng Hospital, Naval Medical University (Second Military Medical University), Shanghai, 200003, China.

出版信息

Lipids Health Dis. 2023 Jul 21;22(1):105. doi: 10.1186/s12944-023-01825-z.

DOI:10.1186/s12944-023-01825-z

PMID:37480069

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10362667/

Abstract

BACKGROUND

Studies have shown that the lipid metabolism mediator leukotriene and prostaglandins are associated with the pathogenesis of allergic rhinitis (AR). The aim of this study was to identify key lipid metabolism-related genes (LMRGs) related to the diagnosis and treatment of AR.

MATERIALS AND METHODS

AR-related expression datasets (GSE75011, GSE46171) were downloaded through the Gene Expression Omnibus (GEO) database. First, weighted gene co-expression network analysis (WGCNA) was used to get AR-related genes (ARRGs). Next, between control and AR groups in GSE75011, differentially expressed genes (DEGs) were screened, and DEGs were intersected with LMRGs to obtain lipid metabolism-related differentially expressed genes (LMR DEGs). Protein-protein interaction (PPI) networks were constructed for these LMR DEGs. Hub genes were then identified through stress, radiality, closeness and edge percolated component (EPC) analysis and intersected with the ARRGs to obtain candidate genes. Biomarkers with diagnostic value were screened via receiver operating characteristic (ROC) curves. Differential immune cells screened between control and AR groups were then assessed for correlation with the diagnostic genes, and clinical correlation analysis and enrichment analysis were performed. Finally, real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was made on blood samples from control and AR patients to validate these identified diagnostic genes.

RESULTS

73 LMR DEGs were obtained, which were involved in biological processes such as metabolism of lipids and lipid biosynthetic processes. 66 ARRGs and 22 hub genes were intersected to obtain four candidate genes. Three diagnostic genes (LPCAT1, SGPP1, SMARCD3) with diagnostic value were screened according to the AUC > 0.7, with markedly variant between control and AR groups. In addition, two immune cells, regulatory T cells (Treg) and T follicular helper cells (TFH), were marked variations between control and AR groups, and SMARCD3 was significantly associated with TFH. Moreover, SMARCD3 was relevant to immune-related pathways, and correlated significantly with clinical characteristics (age and sex). Finally, RT-qPCR results indicated that changes in the expression of LPCAT1 and SMARCD3 between control and AR groups were consistent with the GSE75011 and GSE46171.

CONCLUSION

LPCAT1, SGPP1 and SMARCD3 might be used as biomarkers for AR.

摘要

背景

研究表明，脂质代谢介质白三烯和前列腺素与过敏性鼻炎（AR）的发病机制有关。本研究旨在鉴定与 AR 的诊断和治疗相关的关键脂质代谢相关基因（LMRGs）。

材料和方法

通过基因表达综合数据库（GEO）下载 AR 相关表达数据集（GSE75011、GSE46171）。首先，使用加权基因共表达网络分析（WGCNA）获得 AR 相关基因（ARRGs）。接下来，在 GSE75011 中，在对照组和 AR 组之间筛选差异表达基因（DEGs），并将 DEGs 与 LMRGs 进行交集，获得脂质代谢相关差异表达基因（LMR DEGs）。构建这些 LMR DEGs 的蛋白质-蛋白质相互作用（PPI）网络。然后通过应力、放射度、接近度和边缘渗透分量（EPC）分析识别枢纽基因，并与 ARRGs 相交获得候选基因。通过接收者操作特征（ROC）曲线筛选具有诊断价值的生物标志物。然后评估对照组和 AR 组之间筛选的差异免疫细胞与诊断基因的相关性，并进行临床相关性分析和富集分析。最后，对对照组和 AR 患者的血液样本进行实时荧光定量聚合酶链反应（RT-qPCR）验证这些鉴定的诊断基因。

结果

获得了 73 个 LMR DEGs，这些基因参与了脂质代谢和脂质生物合成过程等生物学过程。将 66 个 ARRGs 和 22 个枢纽基因进行交集，获得了 4 个候选基因。根据 AUC>0.7 筛选出 3 个具有诊断价值的诊断基因（LPCAT1、SGPP1、SMARCD3），在对照组和 AR 组之间存在明显差异。此外，对照组和 AR 组之间有两种免疫细胞，调节性 T 细胞（Treg）和滤泡辅助 T 细胞（TFH）存在明显差异，SMARCD3 与 TFH 显著相关。此外，SMARCD3 与免疫相关途径相关，与临床特征（年龄和性别）显著相关。最后，RT-qPCR 结果表明，LPCAT1 和 SMARCD3 在对照组和 AR 组之间的表达变化与 GSE75011 和 GSE46171 一致。