Objective: To identify the related genes in patients with childhood asthma (CA) based on bioinformatics and immunoassay, and to explore its potential value in the diagnosis of CA. Methods: The GSE27011 data set was downloaded from the Gene Expression Omnibus (GEO) database, and the differentially expressed genes were screened by RStudio. The immune differences between the disease group and the normal group were analyzed respectively. The PPI network was drawn and the Hub genes were screened. The Hub genes were used to select the genes most related to immunity, and the prediction model was constructed by using the screened genes to make a nomogram. Finally, the independent GSE18965 data set was selected for verification. Results: A total of 37 differentially expressed genes were obtained. The difference analysis of immune cells showed that the levels of natural killer cells and plasma cell-like dendritic cells in CA were higher, and the difference of immune function showed that the cytotoxic activity of CA and the level of promoting inflammatory immune function were higher. Ten Hub genes were selected through the PPI network, and then five genes most related to immunity were screened, namely KLRF1, KLRD1, PRF1, IL2RB, and NCAM1. Using five genes to construct models and verify, it was found that KLRF1, KLRD1, PRF1 genes and CA had high predictive diagnostic value. Conclusion: The identified KLRF1, KLRD1 and PRF1 genes may be biomarkers for the diagnosis of CA, and natural killer cells may be a potential therapeutic target for CA.
ZHAO Wei
,
WEI Guangyou
. Identification of genes associated with childhood asthma based on bioinformatics and immunoassay[J]. Journal of Baotou Medical College, 2024
, 40(11)
: 19
-24
.
DOI: 10.16833/j.cnki.jbmc.2024.11.005
[1] Zar HJ, Ferkol TW. The global burden of respiratory disease-Impact on child health[J]. Pediatr Pulmonol, 2014, 49(5): 430-434.
[2] Karimi K, Forsythe P. Natural killer cells in asthma[J]. Front Immunol, 2013, 4: 159.
[3] Fleming M, Fitton CA, Steiner MFC, et al. Educational and health outcomes of children treated for asthma: Scotland-wide record linkage study of 683 716 children[J]. Eur Respir J, 2019, 54(3): 1802309.
[4] Jones H, Lawton A, Gupta A. Asthma attacks in children-challenges and opportunities[J]. Indian J Pediatr, 2022, 89(4): 373-377.
[5] Zhang YM, Moffatt MF, Cookson WOC. Genetic and genomic approaches to asthma: new insights for the origins[J]. Curr Opin Pulm Med, 2012, 18(1): 6-13.
[6] Ivanova O, Richards LB, Vijverberg SJ, et al. What did we learn from multiple omics studies in asthma[J]？Allergy, 2019, 74(11): 2129-2145.
[7] Meyers DA, Bleecker ER, Holloway JW, et al. Asthma genetics and personalised medicine[J]. Lancet Respir Med, 2014, 2(5): 405-415.
[8] Hammad H, Lambrecht BN. The basic immunology of asthma[J]. Cell, 2021, 184(6): 1469-1485.
[9] Clough E, Barrett T. The gene expression omnibus database[M]// Statistical Genomics. New York: Humana Press, 2016: 93-110.
[10] Altman RB. Translational bioinformatics: linking the molecular world to the clinical world[J]. Clin Pharmacol Ther, 2012, 91(6): 994-1000.
[11] Long XR, Xie J, Zhao KT, et al. NK cells contribute to persistent airway inflammation and AHR during the later stage of RSV infection in mice[J]. Med Microbiol Immunol, 2016, 205(5): 459-470.
[12] Jira M, Antosova E, Vondra V, et al. Natural killer and interleukin-2 induced cytotoxicity in asthmatics[J]. Allergy, 1988, 43(4): 294-298.
[13] Lin SJ, Chang LY, Yan DC, et al. Decreased intercellular adhesion molecule-1 (CD54) and L-selectin (CD62L) expression on peripheral blood natural killer cells in asthmatic children with acute exacerbation[J]. Allergy, 2003, 58(1): 67-71.
[14] Qian Q, Chowdhury BP, Sun ZH, et al. Maternal diesel particle exposure promotes offspring asthma through NK cell-derived granzyme B[J]. J Clin Invest, 2020, 130(8): 4133-4151.
[15] Suto Y, Yabe T, Maenaka K, et al. The human natural killer gene complex (NKC) is located on chromosome 12p13.1-p13.2[J]. Immunogenetics, 1997, 46(2): 159-162.
[16] Du ZY, Reed EF, Rajalingam R. Phenotypic diversity of the conserved killer cell lectin-like receptor genes[J]. Hum Immunol, 2005, 66(8): 22.
[17] Roda-Navarro P, Arce I, Renedo M, et al. Human KLRF1, a novel member of the killer cell lectin-like receptor gene family: molecular characterization, genomic structure, physical mapping to the NK gene complex and expression analysis[J]. Eur J Immunol, 2000, 30(2): 568-576.
[18] Bongen E, Vallania F, Utz PJ, et al. KLRD1-expressing natural killer cells predict influenza susceptibility[J]. Genome Med, 2018, 10(1): 45.
[19] Elgizouli M, Logan C, Nieters A, et al. Cord blood PRF1 methylation patterns and risk of lower respiratory tract infections in infants: findings from the Ulm Birth Cohort[J]. Medicine, 2015, 94(1): e332.
[20] Voskoboinik I, Dunstone MA, Baran K, et al. Perforin: structure, function, and role in human immunopathology[J]. Immunol Rev, 2010, 235(1): 35-54.
[21] Willenbring RC, Ikeda Y, Pease LR, et al. Human perforin gene variation is geographically distributed[J]. Mol Genet Genomic Med, 2018, 6(1): 44-55.
[22] Nguyen KD, Vanichsarn C, Nadeau KC. Increased cytotoxicity of CD4+ invariant NKT cells against CD4+CD25hiCD127lo/- regulatory T cells in allergic asthma[J]. Eur J Immunol, 2008, 38(7): 2034-2045.
[23] Arnold V, Balkow S, Staats R, et al. Increase in perforin-positive peripheral blood lymphocytes in extrinsic and intrinsic asthma[J]. Am J Respir Crit Care Med, 2000, 161(1): 182-186.
