| Popis: |
Graves' disease (GD) is an autoimmune disorder characterized by hyperthyroidism resulting from autoantibody-induced stimulation of the thyroid gland. Despite recent advancements in understanding GD's pathogenesis, the molecular processes driving disease progression and treatment response remain poorly understood. In this study, we aimed to identify crucial immunogenic factors associated with GD prognosis and immunotherapeutic response. To achieve this, we implemented a comprehensive screening strategy that combined computational immunogenicity-potential scoring with multi-parametric cluster analysis to assess the immunomodulatory genes in GD-related subtypes involving stromal and immune cells. Utilizing weighted gene co-expression network analysis (WGCNA), we identified co-expressed gene modules linked to cellular senescence and immune infiltration in CD4+ and CD8+ GD samples. Additionally, gene set enrichment analysis enabled the identification of hallmark pathways distinguishing high- and low-immune subtypes. Our WGCNA analysis revealed 21 gene co-expression modules comprising 1,541 genes associated with immune infiltration components in various stages of GD, including T cells, M1 and M2 macrophages, NK cells, and Tregs. These genes primarily participated in T cell proliferation through purinergic signaling pathways, particularly neuroactive ligand-receptor interactions, and DNA binding transcription factor activity. Three genes, namely PRSS1, HCRTR1, and P2RY4, exhibited robustness in GD patients across multiple stages and were involved in immune cell infiltration during the late stage of GD (p |
