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加权基因共表达网络分析揭示了哮喘患者支气管上皮细胞的关键生物标志物和免疫浸润特征。

Weighted gene co-expression network analysis reveals key biomarkers and immune infiltration characteristics for bronchial epithelial cells from asthmatic patients.

机构信息

Respiratory Department, The First People's Hospital of Lanzhou City, Lanzhou, Gansu, China.

Traditional Chinese Medical Hospital of Xinjiang Uygur Autonomous Region, Xinjiang, China.

出版信息

Medicine (Baltimore). 2024 Apr 19;103(16):e37796. doi: 10.1097/MD.0000000000037796.

DOI:10.1097/MD.0000000000037796
PMID:38640283
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11029931/
Abstract

BACKGROUND

Asthma ranks among the most prevalent non-communicable diseases worldwide. Previous studies have elucidated the significant role of the immune system in its pathophysiology. Nevertheless, the immune-related mechanisms underlying asthma are complex and still inadequately understood. Thus, our objective was to investigate novel key biomarkers and immune infiltration characteristics associated with asthma by employing integrated bioinformatics tools.

METHODS

In this study, we conducted a weighted gene co-expression network analysis (WGCNA) to identify key modules and genes potentially implicated in asthma. Functional annotation of these key modules and genes was carried out through gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Additionally, we constructed a protein-protein interaction (PPI) network using the STRING database to identify 10 hub genes. Furthermore, we evaluated the relative proportion of immune cells in bronchial epithelial cell samples from 20 healthy individuals and 88 asthmatic patients using CIBERSORT. Finally, we validated the hub genes and explored their correlation with immune infiltration.

RESULTS

Furthermore, 20 gene expression modules and 10 hub genes were identified herein. Among them, complement component 3 (C3), prostaglandin I2 receptor (PTGIR), parathyroid hormone-like hormone (PTHLH), and C-X3-C motif chemokine ligand 1 (CX3CL1) were closely correlated with the infiltration of immune cells. They may be novel candidate biomarkers or therapeutic targets for asthma. Furthermore, B cells memory, and plasma cells might play an important role in immune cell infiltration after asthma.

CONCLUSIONS

C3, PTGIR, CX3CL1, and PTHLH have important clinical diagnostic values and are correlated with infiltration of multiple immune cell types in asthma. These hub genes, B cells memory, and plasma cells may become important biological targets for therapeutic asthma drug screening and drug design.

摘要

背景

哮喘是全球最常见的非传染性疾病之一。先前的研究已经阐明了免疫系统在其病理生理学中的重要作用。然而,哮喘的免疫相关机制复杂,仍未得到充分理解。因此,我们的目标是通过整合生物信息学工具来研究与哮喘相关的新型关键生物标志物和免疫浸润特征。

方法

在这项研究中,我们进行了加权基因共表达网络分析(WGCNA),以鉴定可能与哮喘相关的关键模块和基因。通过基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析对这些关键模块和基因进行功能注释。此外,我们使用 STRING 数据库构建了蛋白质-蛋白质相互作用(PPI)网络,以识别 10 个枢纽基因。此外,我们使用 CIBERSORT 评估了 20 名健康个体和 88 名哮喘患者的支气管上皮细胞样本中免疫细胞的相对比例。最后,我们验证了枢纽基因,并探索了它们与免疫浸润的相关性。

结果

此外,本研究还鉴定了 20 个基因表达模块和 10 个枢纽基因。其中,补体成分 3(C3)、前列腺素 I2 受体(PTGIR)、甲状旁腺激素样激素(PTHLH)和 C-X3-C 基序趋化因子配体 1(CX3CL1)与免疫细胞的浸润密切相关。它们可能是哮喘的新型候选生物标志物或治疗靶点。此外,B 细胞记忆和浆细胞可能在哮喘后免疫细胞浸润中发挥重要作用。

结论

C3、PTGIR、CX3CL1 和 PTHLH 具有重要的临床诊断价值,与哮喘中多种免疫细胞类型的浸润相关。这些枢纽基因、B 细胞记忆和浆细胞可能成为治疗哮喘药物筛选和药物设计的重要生物学靶点。

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