Du Yiting, Zuo Limin, Xiong Ying, Wang Xuedong, Zou Jun, Xu Hong
Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People's Republic of China.
J Inflamm Res. 2023 Apr 17;16:1653-1669. doi: 10.2147/JIR.S397491. eCollection 2023.
Bronchopulmonary dysplasia (BPD) refers to a chronic lung disease which is commonly observed in preterm infants. It can usually be caused by several pathological processes that endanger the long-term lung development, such as inflammation and immune dysfunction.
In this study, a bioinformatics approach was applied to identify the differentially expressed immune-related genes (DEIRGs). We downloaded the transcriptional profiles (GSE32472 dataset) from the Gene Expression Omnibus (GEO) database and performed gene set enrichment analysis (GSEA). Cell type Identification By Estimating Relative Subsets of RNA Transcripts (CIBERSORT), microenvironment cell populations counter (MCPcounter), and Estimation of STromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) were used for the analysis of the immune cell infiltration landscape of BPD. A weighted co-expression network was subsequently constructed using weighted gene co-expression network analysis (WGCNA) to screen candidate differentially expressed immune related genes (DEIRGs).
GSEA results indicated that immune-related pathways were mainly involved in BPD. Ten significantly different immune cell types were observed between BPD and normal groups. A total of 228 DEGs in the turquoise module were identified, and 31 DEIRGs were further identified. Cluster of the differentiation 8 alpha (CD8A) expression was down-regulated in BPD, and its expression was validated by the GSE25286, GSE25293, GSE99633 datasets and qRT-PCR. In addition, CD8A expression was closely associated with immune cells infiltration, especially T cells CD8 and neutrophil.
A distinct immune cell infiltration landscape was found between BPD and normal group. CD8A can be a novel candidate biomarker for BPD, which plays an essential role in the onset and progress of hyperoxia-related BPD via the disruption of immune cell functions.
支气管肺发育不良(BPD)是一种常见于早产儿的慢性肺部疾病。它通常由多种危及长期肺部发育的病理过程引起,如炎症和免疫功能障碍。
在本研究中,应用生物信息学方法鉴定差异表达的免疫相关基因(DEIRGs)。我们从基因表达综合数据库(GEO)下载了转录谱(GSE32472数据集)并进行基因集富集分析(GSEA)。使用通过估计RNA转录本相对子集鉴定细胞类型(CIBERSORT)、微环境细胞群体计数器(MCPcounter)以及利用表达数据估计恶性肿瘤组织中的基质和免疫细胞(ESTIMATE)来分析BPD的免疫细胞浸润情况。随后使用加权基因共表达网络分析(WGCNA)构建加权共表达网络,以筛选候选差异表达免疫相关基因(DEIRGs)。
GSEA结果表明免疫相关途径主要参与BPD。在BPD组和正常组之间观察到10种显著不同的免疫细胞类型。在绿松石模块中总共鉴定出228个差异表达基因(DEGs),并进一步鉴定出31个DEIRGs。分化簇8α(CD8A)在BPD中的表达下调,其表达通过GSE25286、GSE25293、GSE99633数据集和qRT-PCR得到验证。此外,CD8A表达与免疫细胞浸润密切相关,尤其是T细胞CD8和中性粒细胞。
在BPD组和正常组之间发现了明显不同的免疫细胞浸润情况。CD8A可能是BPD的一种新型候选生物标志物,它通过破坏免疫细胞功能在高氧相关BPD的发生和发展中起重要作用。