诱导痰中MMP12 mRNA表达增加与哮喘患者气道嗜酸性炎症相关:来自生物信息学分析和实验验证的证据
2021/09/24
摘要
背景：哮喘是世界范围内常见的慢性气道炎症性疾病。诱导痰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。
目的：探讨MMP12基因在诱导痰中的表达及其与哮喘气道嗜酸性炎症的关系。
方法：采用R软件、加权基因共表达网络分析(WGCNA)和蛋白相互作用网络构建(PPI)对GSE76262数据集进行分析。用Cytoscape软件(3.8.4版)筛选前10个hub基因。然后，我们通过ROC曲线估计验证了MMP12在另外两个数据集(GSE137268和GSE74075)中的mRNA表达，并通过实时定量反转录聚合酶链反应(qRT-PCR)验证了我们的诱导痰样本。最后，我们探讨了MMP12与哮喘嗜酸性粒细胞相关指标的相关性。
结果：我们通过对GSE76262数据集的表达谱筛选和验证，获得了CCL17、CCL2、CSF1、CCL22、CCR3、CD69、FCGR2B、CD1C、CD1E和MMP12的前10个中心基因。通过对GSE137268和GSE74075数据集的进一步验证，选择MMP12作为候选基因。最后，我们发现MMP12的mRNA表达在哮喘患者诱导痰中显著上调(p <0.05)，且与嗜酸性相关指标显著相关(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：我们的研究成功地识别并证明，MMP12由于其高表达并与嗜酸性粒细胞相关指标相关，是一种潜在的哮喘诊断生物标志物。本研究结果可为今后哮喘的诊断和治疗提供新的思路。
Increased MMP12 mRNA expression in induced sputum was correlated with airway eosinophilic inflammation in asthma patients: Evidence from bioinformatic analysis and experiment verification
Du LJ, Chen FJ, Xu CY, et al
Abstract
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.
Conclusions：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.
背景：哮喘是世界范围内常见的慢性气道炎症性疾病。诱导痰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。
目的：探讨MMP12基因在诱导痰中的表达及其与哮喘气道嗜酸性炎症的关系。
方法：采用R软件、加权基因共表达网络分析(WGCNA)和蛋白相互作用网络构建(PPI)对GSE76262数据集进行分析。用Cytoscape软件(3.8.4版)筛选前10个hub基因。然后，我们通过ROC曲线估计验证了MMP12在另外两个数据集(GSE137268和GSE74075)中的mRNA表达，并通过实时定量反转录聚合酶链反应(qRT-PCR)验证了我们的诱导痰样本。最后，我们探讨了MMP12与哮喘嗜酸性粒细胞相关指标的相关性。
结果：我们通过对GSE76262数据集的表达谱筛选和验证，获得了CCL17、CCL2、CSF1、CCL22、CCR3、CD69、FCGR2B、CD1C、CD1E和MMP12的前10个中心基因。通过对GSE137268和GSE74075数据集的进一步验证，选择MMP12作为候选基因。最后，我们发现MMP12的mRNA表达在哮喘患者诱导痰中显著上调(p <0.05)，且与嗜酸性相关指标显著相关(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：我们的研究成功地识别并证明，MMP12由于其高表达并与嗜酸性粒细胞相关指标相关，是一种潜在的哮喘诊断生物标志物。本研究结果可为今后哮喘的诊断和治疗提供新的思路。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（Gene, 2021, 804.）
（Gene, 2021, 804.）
Increased MMP12 mRNA expression in induced sputum was correlated with airway eosinophilic inflammation in asthma patients: Evidence from bioinformatic analysis and experiment verification
Du LJ, Chen FJ, Xu CY, et al
Abstract
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.
Conclusions：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.
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哮喘的实质破坏：固定气流阻塞和肺功能轨迹
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塑料微粒暴露对正常和哮喘肺生理的有害影响
