Identification of ADAM23 as a Potential Signature for Psoriasis Using Integrative Machine-Learning and Experimental Verification

Abstract

Background Psoriasis is a common chronic, recurrent, and inflammatory skin disease. Identifying novel and potential biomarkers is valuable in the treatment and diagnosis of psoriasis. The goal of this study was to identify novel key biomarkers of psoriasis and analyze the potential underlying mechanisms. Methods Psoriasis-related datasets were downloaded from the Gene Expression Omnibus database to screen differential genes in the datasets. Functional and pathway enrichment analyses were performed on the differentially expressed genes (DEGs). Candidate biomarkers for psoriasis were identified from the GSE30999 and GSE6710 datasets using four machine learning algorithms, namely, random forest (RF), least absolute shrinkage and selection operator (LASSO) logistic regression, weighted gene co-expression network analysis (WGCNA), and support vector machine recursive feature elimination (SVM-RFE), and were validated using the GSE41662 dataset. Next, we used CIBERSORT and single-cell RNA analysis to explore the relationship between ADAM23 and immune cells. Finally, we validated the expression of the identified biomarkers expressions in human and mouse experiments. Results A total of 709 overlapping DEGs were identified, including 426 upregulated and 283 downregulated genes. Enhanced by enrichment analysis, the differentially expressed genes (DEGs) were spatially arranged in relation to immune cell involvement, immune-activating processes, and inflammatory signals. Based on the enrichment analysis, the DEGs were mapped to immune cell involvement, immune-activating processes, and inflammatory signals. Four machine learning strategies and single-cell RNA sequencing analysis showed that ADAM23, a disintegrin and metalloprotease, may be a unique, critical biomarker with high diagnostic accuracy for psoriasis. Based on CIBERSORT analysis, ADAM23 was found to be associated with a variety of immune cells, such as macrophages and mast cells, and it was upregulated in the macrophages of psoriatic lesions in patients and mice. Conclusion ADAM23 may be a potential biomarker in the diagnosis of psoriasis and may contribute to the pathogenesis by regulating immunological activity in psoriatic lesions.

Macrophage Functions in Psoriasis: Lessons from Mouse Models

“…Therefore, modern therapeutic strategies used in psoriasis should take macrophage targeting and modulation into account. Advanced bioinformatic studies followed by validation in imiquimod-treated mice demonstrated that upregulation of ADAM23 metalloprotease in macrophages could be used as a biomarker of psoriasis that is likely involved in its pathogenesis and therefore could also be considered as a predictor of potential targets for biological treatments [98]. Moreover, one can speculate that the expression of ADAM23 enables macrophages to modulate cytokine production by psoriasis-associated effector T cells, as previously shown in the case of dendritic cells [99].…”