ArticleAmerican journal of translational research2025
Exploring the landscape of autoimmune disorder-associated genes and their impact on immune microenvironment in breast cancer patients.
Article in American journal of translational research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectivesBreast cancer (BC) remains a leading cause of cancer-related mortality among women worldwide. Emerging evidence suggests that autoimmune-associated genes may critically influence tumor progression and immune evasion. This study investigates the dysregulation of autoimmune-associated genes in BC and explores their potential roles in immune modulation and tumor progression.
methodsTwo publicly available bulk RNA-sequencing datasets (GSE233242 and GSE227679) were analyzed to identify differentially expressed genes (DEGs) between BC and normal tissues. A curated set of autoimmune-related genes was compiled from multiple databases, including ClinVar, UniProt, OMIM, MedlinePlus, GWAS Catalog, and GeneCards. Enrichment analysis was conducted using KEGG pathways via Enrichr, and protein-protein interaction (PPI) networks were constructed using STRING and Cytoscape to identify hub genes.
resultsOut of 3,676 autoimmune genes, 125 were found to be upregulated and 75 downregulated in BC tissues. Key enriched pathways included Cytokine-cytokine receptor interaction, Chemokine signaling, IL-17 signaling, and PI3K-Akt signaling. Ten hub genes were identified, with CXCR4, MMP9, CTLA4, CD80, and ICOS upregulated, and IL6, KIT, PPARG, SLC2A4, and CEBPA downregulated. CXCR4 and MMP9 overexpression was associated with increased metastasis, while downregulation of KIT and PPARG indicated impaired immune surveillance and poorer prognosis.
conclusionsThis study reveals the pivotal role of autoimmune gene dysregulation in BC progression and immune microenvironment remodeling. Integrating autoimmune gene signatures with transcriptomic data provides novel insights into BC pathogenesis and highlights potential biomarkers and therapeutic targets for immune-based interventions.
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