Identification and mechanistic insights of cell senescence-related genes in psoriasis.

Abstract

Background: Psoriasis is a chronic inflammatory skin disease affecting 2-3% of the global population, characterised by red scaly patches that significantly affect patients' quality of life. Recent studies have suggested that cell senescence, a state in which cells cease to divide and secrete inflammatory mediators, plays a critical role in various chronic diseases, including psoriasis. However, the involvement and mechanisms of action of senescence-related genes in psoriasis remain unclear.

Methods: This study aimed to identify senescence-related genes associated with psoriasis and explore their molecular mechanisms. RNA sequencing data from psoriasis and control samples were obtained from the GEO database. Differential expression analysis was performed using DESeq2 to identify differentially expressed genes (DEGs). The intersection of DEGs with cell senescence-related genes from the CellAge database was used to identify the candidate genes. Protein-protein interaction networks, Gene Ontology, and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to explore the functions and pathways of these genes. Machine learning algorithms, including Least Absolute Shrinkage and Selection Operator (LASSO) regression and Support vector machine-recursive feature elimination (SVE-RFE), were used to select feature genes that were validated by qRT-PCR. Additionally, an immune cell infiltration analysis was performed to understand the roles of these genes in the immune response to psoriasis.

Results: This study identified 4,913 DEGs in psoriasis, of which 46 were related to cell senescence. Machine learning highlighted four key genes, CXCL1, ID4, CCND1, and IRF7, as significant. These genes were associated with immune cell infiltration and validated by qRT-PCR, suggesting their potential as therapeutic targets for psoriasis.

Conclusions: This study identified and validated key senescence-related genes involved in psoriasis, providing insights into their molecular mechanisms and potential therapeutic targets and offering a foundation for developing targeted therapies for psoriasis.