Lu Li-Qun, Liao Wei
Department of Pediatrics, First Hospital Affiliated to Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China.
Department of Pediatrics, Southwest Hospital, The Third Military Medical University, Chongqing 400038, P.R. China.
Mol Med Rep. 2015 Jun;11(6):4197-203. doi: 10.3892/mmr.2015.3277. Epub 2015 Jan 29.
The present study aimed to identify differentially expressed genes (DEGs) associated with pediatric allergic asthma, and to analyze the functional pathways of the selected target genes, in order to explore the pathogenesis of the disease. The GSE18965 gene expression profile was downloaded from the Gene Expression Omnibus database and was preprocessed. This gene expression profile consisted of seven normal samples and nine samples from patients with pediatric allergic asthma. The DEGs between the normal and pediatric allergic asthma samples were screened using limma package in R, and the cut‑off value was set at false discovery rate <0.05 and log fold change >1. Following hierarchical clustering of the DEGs based on the expression profiles, the up‑ and downregulated genes underwent a functional enrichment analysis by topological approach (P<0.05), using the Database for Annotation, Visualization and Integrated Discovery. A total of 127 DEGs were identified between the normal and pediatric allergic asthma samples. The up‑ and downregulated genes were significantly enriched in the actin filament‑based process and the monosaccharide metabolic process, respectively. Seven downregulated DEGs (M6PR, TPP1, GLB1, NEU1, ACP2, LAMP1 and HGSNAT) were identified in the lysosomal pathway, with P=6.4x10(‑9). These results suggested that variation in lysosomal function, triggered by the seven downregulated genes, may lead to aberrant functioning of the T lymphocytes, resulting in asthma. Further research regarding the treatment of pediatric allergic asthma through targeting lysosomal function is required.
本研究旨在鉴定与小儿过敏性哮喘相关的差异表达基因（DEGs），并分析所选靶基因的功能途径，以探索该疾病的发病机制。从基因表达综合数据库下载GSE18965基因表达谱并进行预处理。该基因表达谱由7个正常样本和9个小儿过敏性哮喘患者样本组成。使用R语言中的limma软件包筛选正常样本和小儿过敏性哮喘样本之间的DEGs，截断值设定为错误发现率<0.05且对数变化倍数>1。根据表达谱对DEGs进行层次聚类后，使用注释、可视化和综合发现数据库通过拓扑方法（P<0.05）对上调和下调基因进行功能富集分析。在正常样本和小儿过敏性哮喘样本之间共鉴定出127个DEGs。上调和下调基因分别在基于肌动蛋白丝的过程和单糖代谢过程中显著富集。在溶酶体途径中鉴定出7个下调的DEGs（M6PR、TPP1、GLB1、NEU1、ACP2、LAMP1和HGSNAT），P = 6.4x10(-9)。这些结果表明，由这7个下调基因引发的溶酶体功能变化可能导致T淋巴细胞功能异常，从而引发哮喘。需要进一步研究通过靶向溶酶体功能来治疗小儿过敏性哮喘。
