CDC167 exhibits potential as a biomarker for airway inflammation in asthma

IF 2.7 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Mammalian Genome Pub Date : 2024-04-05 DOI:10.1007/s00335-024-10037-4
Yukai Zhong, Qiong Wu, Li Cai, Yuanjing Chen, Qi Shen
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Abstract

Current asthma treatments have been discovered to decrease the risk of disease progression. Herein, we aimed to characterize novel potential therapeutic targets for asthma. Differentially expressed genes (DEGs) for GSE64913 and GSE137268 datasets were characterized. Weighted correlation network analysis (WGCNA) was used to identify trait-related module genes within the GSE67472 dataset. The intersection of the module genes of interest, as well as the DEGs, comprised the key module genes that underwent additional candidate gene screening using machine learning. In addition, a bioinformatics-based approach was used to analyze the relative expression levels, diagnostic values, and reverently enriched pathways of the screened candidate genes. Furthermore, the candidate genes were silenced in asthmatic mice, and the inflammation and lung injury in the mice were validated. A total of 1710 DEGs were characterized in GSE64913 and GSE137268 for asthma patients. WGCNA identified 2367 asthma module genes, of which 285 overlapped with 1710 DEGs. Four candidate genes, CDC167, POSTN, SEC14L1, and SERPINB2, were validated using the intersection genes of three machine learning algorithms, including Least Absolute Shrinkage and Selection Operator, Random Forest, and Support Vector Machine. All the candidate genes were significantly upregulated in asthma patients and demonstrated diagnostic utility for asthma. Furthermore, silencing CDC167 reduced the levels of inflammatory cytokines significantly and alleviated lung injury in ovalbumin (OVA)-induced asthmatic mice. Our study demonstrated that CDC167 exhibits potential as diagnostic markers and therapeutic targets for asthma patients.

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CDC167 具有作为哮喘气道炎症生物标记物的潜力
目前发现的哮喘治疗方法可以降低疾病恶化的风险。在此,我们旨在确定哮喘的新型潜在治疗靶点。我们对 GSE64913 和 GSE137268 数据集的差异表达基因(DEGs)进行了表征。加权相关网络分析(WGCNA)用于识别 GSE67472 数据集中与性状相关的模块基因。感兴趣的模块基因和 DEGs 的交叉点构成了关键模块基因,这些基因通过机器学习进行了额外的候选基因筛选。此外,还采用了一种基于生物信息学的方法来分析筛选出的候选基因的相对表达水平、诊断价值和富集途径。此外,还在哮喘小鼠体内沉默了候选基因,并对小鼠的炎症和肺损伤进行了验证。在哮喘患者的 GSE64913 和 GSE137268 中,共鉴定出 1710 个 DEGs。WGCNA 发现了 2367 个哮喘模块基因,其中 285 个与 1710 个 DEG 重叠。CDC167、POSTN、SEC14L1 和 SERPINB2 这四个候选基因通过三种机器学习算法(包括最小绝对收缩和选择操作器、随机森林和支持向量机)的交叉基因进行了验证。所有候选基因都在哮喘患者中明显上调,并显示出对哮喘的诊断作用。此外,在卵清蛋白(OVA)诱导的哮喘小鼠中,沉默 CDC167 能明显降低炎性细胞因子的水平,减轻肺损伤。我们的研究表明,CDC167 有可能成为哮喘患者的诊断标志物和治疗靶点。
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来源期刊
Mammalian Genome
Mammalian Genome 生物-生化与分子生物学
CiteScore
4.00
自引率
0.00%
发文量
33
审稿时长
6-12 weeks
期刊介绍: Mammalian Genome focuses on the experimental, theoretical and technical aspects of genetics, genomics, epigenetics and systems biology in mouse, human and other mammalian species, with an emphasis on the relationship between genotype and phenotype, elucidation of biological and disease pathways as well as experimental aspects of interventions, therapeutics, and precision medicine. The journal aims to publish high quality original papers that present novel findings in all areas of mammalian genetic research as well as review articles on areas of topical interest. The journal will also feature commentaries and editorials to inform readers of breakthrough discoveries as well as issues of research standards, policies and ethics.
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