Xie Lianhua, Lu Shuxian, Guo Fangyang, Zhang Yifeng, Liu Qian
Discipline of Chinese and Western Integrative Medicine, Jiangxi University of Traditional Chinese Medicine, Integrated Chinese and Western Medicine Institute for Children Health & Drug Innovation, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China.
Medical Transformation Center, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2025 Aug;41(8):695-705.
Objective Through integrative bioinformatics analysis of multi-source transcriptomic data, potential biomarkers to asthma epithelial cells were identified. The expression of these candidate target was subsequently validated in lung tissues and epithelial cells from asthma models. Methods The gene expression profile data of epithelial cells from three asthma patient cohorts and corresponding healthy controls were integrated from the Gene Expression Omnibus (GEO) database. Differential expression analysis and gene co-expression network analysis were performed to identify key genes and biological pathways associated with asthma. The key genes were validated in lung tissues and epithelial cells in asthma animal models. Results Differential gene expression analysis revealed 1121 upregulated and 1484 downregulated genes in epithelial cells from asthma patients compared with healthy controls. The biological pathway enrichment analysis revealed that the upregulated genes were mainly involved in glycosylation processes, whereas the downregulated genes were mainly associated with immune cell differentiation process. The gene co-expression network analysis revealed that module 9, enriched in glycosylation-related pathways, was significantly positively correlated with asthma, whereas module 17, associated with insulin and other signaling pathways, showed a significant negative correlation with asthma. We identified the genes of polypeptide N-acetylgalactosaminyltransferase 5 (GALNT5), pyrroline-5-carboxylate reductase 1 (PYCR1), and carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) as key genes within module 9, all of which were significantly upregulated in asthma. Finally, we validated that the expression levels of GALNT5, PYCR1, and CEACAM5 were significantly upregulated in epithelial cells from asthmatic lung tissue. Additionally, using a rat asthma model, we further confirmed that the protein levels of these three genes were significantly upregulated in lung tissues of the model group. Conclusion Through data integration and experimental validation, this study identified key genes and biological pathways closely associated with asthma pathogenesis. These findings provide a novel theoretical basis and potential targets for the diagnosis and treatment of asthma.
目的 通过对多源转录组数据进行整合生物信息学分析，鉴定哮喘上皮细胞的潜在生物标志物。随后在哮喘模型的肺组织和上皮细胞中验证这些候选靶点的表达。方法 从基因表达综合数据库（GEO）中整合三个哮喘患者队列及相应健康对照的上皮细胞基因表达谱数据。进行差异表达分析和基因共表达网络分析，以鉴定与哮喘相关的关键基因和生物学途径。在哮喘动物模型的肺组织和上皮细胞中验证关键基因。结果 差异基因表达分析显示，与健康对照相比，哮喘患者上皮细胞中有1121个基因上调，1484个基因下调。生物学途径富集分析表明，上调基因主要参与糖基化过程，而下调基因主要与免疫细胞分化过程相关。基因共表达网络分析显示，富集于糖基化相关途径的模块9与哮喘呈显著正相关，而与胰岛素及其他信号通路相关的模块17与哮喘呈显著负相关。我们确定多肽N-乙酰半乳糖胺基转移酶5（GALNT5）、脯氨酸-5-羧酸盐还原酶1（PYCR1）和癌胚抗原相关细胞粘附分子5（CEACAM5）基因是模块9中的关键基因，在哮喘中均显著上调。最后，我们验证了GALNT5、PYCR1和CEACAM5在哮喘肺组织上皮细胞中的表达水平显著上调。此外，使用大鼠哮喘模型，我们进一步证实这三个基因的蛋白水平在模型组肺组织中显著上调。结论 通过数据整合和实验验证，本研究鉴定了与哮喘发病机制密切相关的关键基因和生物学途径。这些发现为哮喘的诊断和治疗提供了新的理论基础和潜在靶点。
