Background and Aims: Psoriatic arthritis is a chronic inflammatory disease characterized by the interplay of genetic, immune, and environmental factors, primarily affecting the joints and skin. Central to its pathogenesis is the dysregulated chemokine signaling pathway, which orchestrates the recruitment of immune cells to sites of inflammation. Chemokines such as CXCL۱۰ and CCL۲, along with their respective receptors (e.g., CXCR۳ and CCR۵), drive persistent inflammation, tissue damage, and joint destruction. This pathway not only contributes to the disease's clinical manifestations but also serves as a potential target for therapeutic interventions, highlighting its importance in understanding and managing PsA. Methods: Bulk RNA sequencing data were retrieved from the GEO repository and analyzed using the GEO۲R tool. Identified differentially expressed genes were employed to construct and study a protein-protein interaction network using the STRING database and Cytoscape software. Functional enrichment analysis was conducted via the Enrichr platform to explore the biological roles of key clusters. This method provides valuable insights into the molecular differences between healthy and psoriatic arthritis-affected skin, paving the way for potential therapeutic advancements. Results: Our analysis identified EGF, MMP۹, MUC۱, STAT۱, CXCL۸, and CXCL۱۰ as the most central proteins among the differentially expressed genes. To uncover specific gene clusters driving distinct pathways, we utilized the Gephi application. Using its modularity algorithm, we identified five distinct functional protein clusters. Among these clusters, Cluster ۲—comprising CCL۳, FCGR۳B, CCL۴, FCGR۳A, CD۸۰, and CCR۷—was identified as being associated with the chemokine signaling pathway through enrichment analysis. Within this cluster, CCL۳ emerged as the most central gene based on metrics such as closeness, harmonic closeness, and eigenvector centrality. Notably, CCL۳ was found to be connected with proteins such as GZMB, CD۳۸, PLEK, CCR۷, CD۸۰, IL۷R, CD۲۸, FCGR۳B, and CTLA۴. Conclusion: Our analysis highlights critical molecular differences and key signaling pathways between healthy and psoriatic arthritis-affected skin. The identification of central proteins such as CCL۳ and its connections within the chemokine signaling pathway provides insights into the pathophysiology of psoriatic arthritis. These findings
