Zou Zhenzhuang, Li Yunrong, Liu Jiaying, Huang Bo
Department of Pediatrics, The Fifth Affiliated Hospital of Zunyi Medical University, No.1439 Zhufeng Avenue, Doumen District, Zhuhai, 519100, Guangdong, People's Republic of China.
Department of Pediatrics, Women and Children, Health Institute of Futian Shenzhen, Shenzhen, 518000, China.
Mol Biotechnol. 2024 Sep 18. doi: 10.1007/s12033-024-01281-9.
The objective of this study was to identify and characterize oxidative stress (OS)-related biomarkers in bronchopulmonary dysplasia (BPD) through a combination of bioinformatics analyses and wet experiments. The study utilized the Gene Expression Omnibus database to obtain the mRNA expression profile dataset GSE32472. Differential expression analysis and functional enrichment analysis were employed to investigate the role of OS-related genes in BPD. Gene Ontology Function Enrichment Analysis and Gene Set Enrichment Analysis were conducted to understand the mechanisms behind the signature. Protein-protein interaction analysis to identify hub genes in BPD, and predictions were made for microRNAs (miRNAs), transcription factors (TFs), and potential medications targeting these genes. CIBERSORT was utilized to investigate the correlation between hub genes and the infiltration of immune cells. Hub genes were ultimately determined and confirmed using expression analysis, correlation analysis, receiver operating characteristic (ROC) analysis, and quantitative real-time PCR (qRT-PCR). A novel OS-related gene signature (ARG1, CSF3R, IL1R1, IL1R2, MMP9, RETN, S100A12, and SOCS3) was constructed for the prediction of BPD. We identified 18 miRNAs, 14 TFs, and 30 potential medications targeting these genes. ROC analysis further validated that these genes could diagnose BPD with high specificity and sensitivity. The qRT-PCR revealed that IL1R1 and ARG1 were highly expressed in the lung tissue of the model group, while the expressions of RETN, SOCS3, IL1R2, and MMP9 were decreased. This study demonstrated that ARG1, CSF3R, IL1R1, IL1R2, MMP9, RETN, S100A12, and SOCS3 may serve as potential diagnostic biomarkers in BPD. Furthermore, a significant association between IL1R1 and the pathogenesis of BPD is observed.
本研究的目的是通过生物信息学分析和湿实验相结合的方法，鉴定并表征支气管肺发育不良（BPD）中与氧化应激（OS）相关的生物标志物。该研究利用基因表达综合数据库获取mRNA表达谱数据集GSE32472。采用差异表达分析和功能富集分析来研究OS相关基因在BPD中的作用。进行基因本体功能富集分析和基因集富集分析以了解该特征背后的机制。通过蛋白质-蛋白质相互作用分析来鉴定BPD中的枢纽基因，并对靶向这些基因的微小RNA（miRNA）、转录因子（TF）和潜在药物进行预测。利用CIBERSORT研究枢纽基因与免疫细胞浸润之间的相关性。最终通过表达分析、相关性分析、受试者工作特征（ROC）分析和定量实时PCR（qRT-PCR）确定并确认了枢纽基因。构建了一个用于预测BPD的新型OS相关基因特征（ARG1、CSF3R、IL1R1、IL1R2、MMP9、RETN、S100A12和SOCS3）。我们鉴定出了18个miRNA、14个TF和30种靶向这些基因的潜在药物。ROC分析进一步验证了这些基因能够以高特异性和敏感性诊断BPD。qRT-PCR显示，模型组肺组织中IL1R1和ARG1高表达，而RETN、SOCS3、IL1R2和MMP9的表达降低。本研究表明，ARG1、CSF3R、IL1R1、IL1R2、MMP9、RETN、S100A12和SOCS3可能作为BPD潜在的诊断生物标志物。此外，还观察到IL1R1与BPD发病机制之间存在显著关联。
