Identification and clinical implications of immune-related hub genes in psoriasis

Clinical Snapshot

Key Findings

• P Value: Not specified

• Effect Size: AUC > 0.9 for within-sample discrimination

• Primary Outcome: Six immune-related hub genes identified: CLEC7A, CXCL1, IRF1, S100A12, S100A8, S100A9

• Nnt Or Sensitivity: AUC > 0.9 indicates excellent discriminatory ability

• Confidence Interval: Not reported

Clinical Application

Limited immediate clinical application as gene expression profiling not routinely available in clinical practice Potential relevance for PBS-funded biologic therapies (adalimumab, etanercept, ustekinumab) if validated as predictive biomarkers; would require TGA approval for diagnostic use Patients with psoriasis, particularly those being considered for or receiving biologic therapy

Abstract

BACKGROUND: Psoriasis, a chronic inflammatory skin disease affecting 2-3% of the global population, is driven by dysregulated immune responses. Despite advancements in biologic therapies, treatment challenges persist due to high recurrence rates. This study aimed to identify immune-related hub genes and elucidate their clinical implications in psoriasis pathogenesis and therapy. METHODS: Multiple microarray datasets from psoriasis patients (GSE30999, GSE106992, GSE14905, GSE78097, and GSE117468) were obtained to identify immune-key genes by differential gene analysis and Weighted Gene Co-expression Network Analysis (WGCNA). Subsequently, immune-related hub genes were identified using the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and Protein-Protein Interaction (PPI) networks, with further validation through Gene Set Enrichment Analysis (GSEA) and Receiver Operating Characteristic (ROC) curves to assess exploratory within-sample discrimination. Pearson correlation analysis evaluated the relationship between hub genes, skin lesion severity, and treatment outcomes. The study also conducted immune infiltration by using the Cell-type Identification by Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm and identified potential therapeutic targets by the Drug-Gene Interaction Database (DGIdb). RESULTS: Thirty-one immune-related key genes were identified, and six hub genes (CLEC7A, CXCL1, IRF1, S100A12, S100A8, S100A9) were validated as central players in immune signaling pathways. These genes exhibited within-sample discrimination (AUC > 0.9) and correlated with disease severity and biological therapy efficacy. Immune infiltration analysis revealed increased activated memory CD4+ T cells and M1 macrophages in lesional skin, which was strongly associated with hub gene expression. Additionally, drug-gene interaction analysis identified potential therapeutic agents targeting these genes. CONCLUSION: This study identified six immune-related hub genes that were closely linked to the severity of psoriasis, the effectiveness of biological treatments, and infiltrated activated memory CD4+ T cells and M1 macrophages. Our findings elucidate a novel immune-related hub gene network in psoriasis and provide potential targets for the development and application of biologics.

References

1. 1.Sun, Y., Zhou, Z., Mao, Y., Liu, N., Li, Y., & Fang, W. (2026). Identification and clinical implications of immune-related hub genes in psoriasis. PLoS One. https://doi.org/10.1371/journal.pone.0347536