Background

Asthma is a common chronic airway inflammatory disease worldwide. Studies on gene expression profiles in induced sputum may provide noninvasive diagnostic biomarkers and therapeutic targets for asthma.

Objective

To investigate mRNA expression of MMP12 in induced sputum and its relationship with asthma airway eosinophilic inflammation.

Methods

GSE76262 dataset was analyzed using R software, weighted gene coexpression network analysis (WGCNA), and protein–protein interaction (PPI) network construction. The top ten hub genes were screened with Cytoscape software (version 3.8.4). We then verified the mRNA expression of MMP12 in two other datasets (GSE137268 and GSE74075) via ROC curve estimates and our induced sputum samples using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Finally, we explored the correlation between MMP12 with asthmatic eosinophilic-related indicators.

Results

We obtained the top ten hub genes, namely, CCL17, CCL2, CSF1, CCL22, CCR3, CD69, FCGR2B, CD1C, CD1E, and MMP12 via expression profile screening and validation on the GSE76262 dataset. MMP12 was selected as the candidate gene through further validation on GSE137268 and GSE74075 datasets. Finally, we demonstrated that the mRNA expression of MMP12 is significantly upregulated in induced sputum of asthmatic patients (p<0.05) and significantly correlated with eosinophilic-related indicators (p<0.05). These findings indicated that MMP12 can act as a diagnostic biomarker for asthma.

Conclusion

Our study successfully identified and demonstrated that MMP12 is a potential diagnostic biomarker for asthma due to its high expression and association with eosinophilic-related indicators. The results of this study can provide novel insights into asthmatic diagnosis and therapy in the future.

中文翻译：

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诱导痰中MMP12 mRNA表达增加与哮喘患者气道嗜酸性粒细胞炎症相关：来自生物信息学分析和实验验证的证据

背景

哮喘是世界范围内常见的慢性气道炎症性疾病。对诱导痰中基因表达谱的研究可能为哮喘提供无创诊断生物标志物和治疗靶点。

客观的

探讨诱导痰中MMP12 mRNA的表达及其与哮喘气道嗜酸性粒细胞炎症的关系。

方法

使用 R 软件、加权基因共表达网络分析 (WGCNA) 和蛋白质-蛋白质相互作用 (PPI) 网络构建分析 GSE76262 数据集。用Cytoscape软件（3.8.4版）筛选出前十个hub基因。然后，我们通过 ROC 曲线估计和我们使用实时定量逆转录聚合酶链反应 (qRT-PCR) 的诱导痰样本验证了其他两个数据集（GSE137268 和 GSE74075）中 MMP12 的 mRNA 表达。最后，我们探讨了 MMP12 与哮喘嗜酸性粒细胞相关指标之间的相关性。

结果

我们通过对 GSE76262 数据集的表达谱筛选和验证，获得了前十位的枢纽基因，即 CCL17、CCL2、CSF1、CCL22、CCR3、CD69、FCGR2B、CD1C、CD1E 和 MMP12。通过对 GSE137268 和 GSE74075 数据集的进一步验证，MMP12 被选为候选基因。最后，我们证明 MMP12 的 mRNA 表达在哮喘患者的诱导痰中显着上调（p <0.05）并且与嗜酸性粒细胞相关指标显着相关（p <0.05）。这些发现表明 MMP12 可以作为哮喘的诊断生物标志物。

结论

我们的研究成功鉴定并证明 MMP12 是一种潜在的哮喘诊断生物标志物，因为它的高表达和与嗜酸性粒细胞相关指标的关联。这项研究的结果可以为未来的哮喘诊断和治疗提供新的见解。