Identification of potential biomarkers and therapeutic targets in psoriasis based on NF-κB pathway-related genes

Abstract

Psoriasis, a common chronic and relapsing inflammatory skin disease, requires the identification of new potential biomarkers to improve its diagnosis and treatment. Dysregulation of the Nuclear factor kappa B (NF-κB) signaling pathway is a hallmark of chronic inflammatory diseases. Accordingly, this study aims to identify NF-κB-related biomarkers for psoriasis diagnosis and treatment. Psoriasis-related datasets were downloaded from the Gene Expression Omnibus to screen for differentially expressed genes (DEGs). The intersection of DEGs with NF-κB-related genes yielded NF-κB_DEGs. A protein-protein interaction network was constructed for NF-κB_DEGs, and hub genes were identified using the MCODE plugin. Through LASSO regression, NF-κB-related characteristic genes for psoriasis were identified and a diagnostic model was developed. This model was validated using the GSE13355 and GSE30999 datasets. Disparities in immune cell infiltration between control and psoriasis groups were assessed via single-sample gene set enrichment analysis. Lastly, we predicted functionally similar genes, related pathways, transcription factors (TFs), microRNAs (miRNAs), and potential therapeutic drugs for the characteristic genes. We uncovered four NF-κB-associated genes—LYN, MALT1, MYD88, and PTGS2—that hold significant diagnostic value for psoriasis. A diagnostic model leveraging these genes exhibited high reliability and effectiveness in both training and validation datasets. Immune profiling revealed marked differences between psoriasis and control groups, with substantial enrichment of dendritic cells (DCs), macrophages, B cells, and T cells in psoriasis samples. We also identified 20 genes functionally related to our characteristic genes, which were primarily involved in pathways such as IκB kinase/NF-κB signaling and Toll-like receptor signaling. Furthermore, we predicted 70 TFs (including SP1, FOS, and JUN) and 17 miRNAs (including hsa-let-7b, hsa-miR-30a, and hsa-miR-155) associated with these genes. Among potential therapeutic candidates, Quercetin emerged as the most promising, scoring highest in our comprehensive evaluation. Our study identified four potential biomarkers—LYN, MALT1, MYD88, and PTGS2—which hold considerable value for the diagnosis and therapy of psoriasis.