Identification of Immunological Biomarkers of Atopic Dermatitis by Integrated Analysis to Determine Molecular Targets for Diagnosis and Therapy.

ABSTRACT

PURPOSE: Atopic dermatitis (AD) is a common chronic inflammatory skin disorder associated with immune dysregulation and barrier dysfunction. In this study, we investigated immunological biomarkers for AD diagnosis and treatment using CIBERSORT to identify immune cell infiltration characteristics. PATIENTS AND METHODS: Common differentially expressed genes (DEGs) of lesioned (LS) vs non-lesioned (NL) groups were obtained from public datasets (GSE140684 and GSE99802). We performed functional enrichment analysis and selected hub genes from the protein-protein interaction (PPI) network. The hub genes were then subjected to transcription factor (TF), microRNA (miRNA), long non-coding RNA (lncRNA), drug interaction, and protein subcellular localization analyses. We also performed correlation analysis on differentially expressed immune cells, TFs, and hub genes. Receiver operating characteristic (ROC) curve analysis and binomial least absolute shrinkage and selection operator (LASSO) regression analysis were employed to assess the expression of hub genes in the GSE99802, GSE140684, GSE58558, GSE120721, and GSE36842 datasets. RESULTS: We identified 238 common DEGs and 25 hub genes. Additionally, we predicted TFs, miRNAs, lncRNA, drugs, and protein subcellular localizations. The proportions of activated dendritic cells (DCs) and CD4+ memory T cells were relatively high in the LS skin. Expression levels of the TF FOXC1 were negatively correlated with target genes and the abundance of two immune cell types. The LASSO model showed that GZMB, CXCL1, and CD274 are candidate diagnostic biomarkers. CONCLUSION: Our study suggests that downregulated expression of FOXC1 expression may enhance the levels of chemokines, chemokine receptors, T cell receptor signaling molecules, activating CD4+ memory T cells and DCs in AD.