Transcriptomic Analysis Reveals an Adaptive Immune and Cytokine Signaling Signature in Canine Lupus

Background: Lupus in dogs represents a significant veterinary health challenge that impacts quality of life and requires innovative treatment strategies. This study aims to utilize microarray data analysis to identify the primary pathways and proteins associated with the disease, proposing promising druggable targets. Methods: Microarray data related to canine lupus samples were retrieved from the GEO NCBI database (accession numbers GSE۱۶۰۲۶۰ and GSE۱۸۰۲۷۶). Differential gene expression analysis was performed using GEO۲R to identify the top differentially expressed genes between normal and diseased groups. A Venn diagram was employed to determine common proteins across the two datasets. Subsequently, Gene Ontology enrichment analysis and protein-protein interaction (PPI) network analysis were conducted using R Studio and Cytoscape, respectively. Druggability was assessed for the common interactome across the two datasets using DGIdb. Results: The results revealed significant enrichment in the adaptive immune response (FDR ۲.۶e-۰۳, ۶ genes) and the cytokine-mediated signaling pathway (FDR ۱.۵e-۰۳, ۴ genes), with key genes including CD۳E, CD۸A, and CXCL۱۰. PPI network analysis identified central nodes, including CCL۵ and CD۸A, indicating critical interaction hubs in lupus pathology. Druggability analysis identified TNFRSF۱۷, CD۳E, CCL۵, IL۲۱R, and CXCL۱۰ as promising druggable targets within the common interactome. Conclusions: This investigation has effectively delineated a putative signaling pathway implicated in lupus within canine species, concurrently proposing a suite of novel drug targets. These findings present promising alternatives to traditional therapeutic modalities (cortisone and antimicrobial treatment), thereby facilitating the development of innovative therapeutic strategies.

کلیدواژه ها:

DEG ، Bioinformatics ، PPI ، Canine ، Lupus