Health science reports · 2025
Identification of Cuproptosis-Related Gene Clusters in Behçet's Disease and Its Immunological Profiles by Bioinformatics Analysis.
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Chen Si, Nie Rui, Wang Yan, Luan Haixia, Wang Chao, Gui Yuan, Zeng Xiaoli, Yuan Hui
Аннотация
BACKGROUND AND AIMS: Behçet's disease (BD) is a chronic inflammatory vasculitis marked by immune cell abnormalities and clinical variability. The recently discovered type of programmed cell death, termed cuproptosis, appears to be involved in multiple disease mechanisms. Thus, this study aimed to elucidate the involvement of cuproptosis-related genes (CRGs) in BD.
METHODS: We obtained two bipolar disorder datasets from the gene expression omnibus repository and pinpointed differentially expressed genes linked to cuproptosis (CuDEGs) from a selection of 52 CRGs. Subsequently, machine learning methods were employed to identify hub CuDEGs. We analyzed 44 BD specimens to identify two unique subgroups derived from these hub CuDEGs. Additionally, we conducted gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment studies, along with gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA), and assessed immune cell infiltration and immune function-related cells.
RESULTS: A total of 15 CuDEGs were discovered. Using machine learning algorithms, six hub CuDEGs were identified: ANKRD9, COX11, MT1G, MT2A, MT4, and TYR. These hub CuDEGs generally showed elevated expression levels in BD samples, leading to the identification of two CuDEGs-related subclusters. Cluster 2 had higher expression of most hub CuDEGs. GSEA and GSVA results demonstrated that different hub CuDEGs were enriched in distinct pathways. Analyses of immune infiltration and function-related cells revealed that hub CuDEGs were involved in various immune response processes, such as macrophage and neutrophil activation, highlighting significant differences in immune regulation among the hub CuDEGs.
CONCLUSION: This study demonstrates that CuDEGs are differentially expressed in BD and are associated with immune activity and pathway alterations. These findings suggest that cuproptosis may contribute to BD progression through the modulation of immune responses. Further experimental studies are needed to confirm these bioinformatics-based findings and explore their therapeutic potential.
METHODS: We obtained two bipolar disorder datasets from the gene expression omnibus repository and pinpointed differentially expressed genes linked to cuproptosis (CuDEGs) from a selection of 52 CRGs. Subsequently, machine learning methods were employed to identify hub CuDEGs. We analyzed 44 BD specimens to identify two unique subgroups derived from these hub CuDEGs. Additionally, we conducted gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment studies, along with gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA), and assessed immune cell infiltration and immune function-related cells.
RESULTS: A total of 15 CuDEGs were discovered. Using machine learning algorithms, six hub CuDEGs were identified: ANKRD9, COX11, MT1G, MT2A, MT4, and TYR. These hub CuDEGs generally showed elevated expression levels in BD samples, leading to the identification of two CuDEGs-related subclusters. Cluster 2 had higher expression of most hub CuDEGs. GSEA and GSVA results demonstrated that different hub CuDEGs were enriched in distinct pathways. Analyses of immune infiltration and function-related cells revealed that hub CuDEGs were involved in various immune response processes, such as macrophage and neutrophil activation, highlighting significant differences in immune regulation among the hub CuDEGs.
CONCLUSION: This study demonstrates that CuDEGs are differentially expressed in BD and are associated with immune activity and pathway alterations. These findings suggest that cuproptosis may contribute to BD progression through the modulation of immune responses. Further experimental studies are needed to confirm these bioinformatics-based findings and explore their therapeutic potential.