文献类型：期刊文献

英文题名：Screening and Validation of Potential Biomarkers of Immune Cells in Childhood Asthma Patients via Mendelian Randomization and Machine Learning

作者：Zhang, Yang[1,2,4];Hai, Yang[1,2,3];Song, Bangguo[4];Xu, Jing[1,2,3];Cao, Liangjia[5];Yasen, Rukeye[5];Xu, Wenjuan[5];Zhang, Jiaxuan[5];Hu, Jihong[6]

第一作者：张扬

通信作者：Hu, JH[1]

机构：[1]Gansu Univ Chinese Med, Sci Res & Expt Ctr, Lanzhou, Peoples R China;[2]Gansu Univ Chinese Med, Key Lab Dunhuang Med, Minist Educ, Lanzhou, Peoples R China;[3]Gansu Univ Chinese Med, Res Ctr Tradit Chinese Med, Lanzhou, Gansu, Peoples R China;[4]Gansu Univ Chinese Med, Clin Coll Chinese Med, Lanzhou, Peoples R China;[5]Gansu Univ Chinese Med, Coll Publ Hlth, Lanzhou, Peoples R China;[6]Gansu Univ Chinese Med, Lab & Simulat Training Ctr, Lanzhou 73000, Gansu, Peoples R China

第一机构：甘肃中医药大学科研实验中心（甘肃省中医药标准化技术委员会秘书处）

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Lab & Simulat Training Ctr, Lanzhou 73000, Gansu, Peoples R China.|[10735]甘肃中医药大学;

年份：2025

卷号：18

起止页码：2583

外文期刊名：JOURNAL OF INFLAMMATION RESEARCH

收录：;Scopus(收录号：2-s2.0-85219480005);WOS:【SCI-EXPANDED(收录号:WOS:001428649600001)】；

基金：This study was supported by grants from the National Natural Science Foundation of China (grant number 81960614) ; Open Subjects of the Key Laboratory of Dunhuang Medicine, Ministry of Education (DHYX20-17) ; Open Subjects of the Research Center of Traditional Chinese Medicine, Gansu Province (ZYZX-2023-05) ; Gansu Provincial Administration of Traditional Chinese Medicine Scientific Research Project (GZKP-2023-42) ; Scientific Research and Innovation Fund Project of Gansu University of Chinese Medicine (2023KCYB-7) ; General project of Gansu Provincial Joint Scientific Research Fund (No. 24JRRA880) .

语种：英文

外文关键词：childhood asthma; immune cells; Mendelian randomization; biomarker; key genes

摘要：Purpose: Asthma is one of the most common chronic respiratory diseases affecting children, and there is currently no clear remedy. Immune cells play a key role in childhood asthma. Therefore, a deeper investigation of the correlation between immune cells and childhood asthma could lead to a better understanding of asthma's origin, the identification of potential treatment targets, and the development of personalized treatment strategies. Patients and Methods: We used a two-sample Mendelian randomization (MR) analysis to investigate the possible causal relationship between childhood asthma and a total of 731 immune cells, including B cell (190), Maturation stages of T cell (79), Monocyte (43), Myeloid cell (64), TBNK (124), Treg (167), and CDC (64). LASSO logistic regression and SVM algorithms were used to identify key genes associated with childhood asthma. Specific signaling pathways associated with these key genes were further explored through gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA). Subsequently, the four key genes FCGR3A, TCTN3, ALOX5, and IL4R were verified in an established asthma mouse model using quantitative real-time PCR and Western blotting. Results: MR analysis showed that 60 immune cells were associated with childhood asthma, of which 32 were associated with high risk and 28 were associated with low risk. LASSO logistic regression and SVM algorithm identified six key genes that affect childhood asthma as ATF4, FCGR3A, GAS5, MGAT3, TAB1, and TCTN3. In addition, four genes, FCGR3A, TCTN3, ALOX5, and IL4R, were verified through animal experiments. Conclusion: Our findings confirmed that immune cells contribute to childhood asthma, highlighting the importance of key genes in the role of the immune microenvironment in this disease. These insights provide a new path for the exploration of the biological underpinnings of childhood asthma and the development of early intervention therapies.