Chen Si, Nie Rui, Wang Yan, Luan Haixia, Wang Chao, Gui Yuan, Zeng Xiaoli, Yuan Hui
Department of Clinical Laboratory Beijing Anzhen Hospital, Capital Medical University Beijing China.
Health Sci Rep. 2025 Aug 4;8(8):e71098. doi: 10.1002/hsr2.71098. eCollection 2025 Aug.
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.
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.
A total of 15 CuDEGs were discovered. Using machine learning algorithms, six hub CuDEGs were identified: , , , , , and . 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.
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.
白塞病（BD）是一种慢性炎症性血管炎，其特征为免疫细胞异常和临床变异性。最近发现的一种程序性细胞死亡类型，称为铜死亡，似乎参与了多种疾病机制。因此，本研究旨在阐明铜死亡相关基因（CRGs）在白塞病中的作用。
我们从基因表达综合数据库中获取了两个双相情感障碍数据集，并从52个CRGs中筛选出与铜死亡相关的差异表达基因（CuDEGs）。随后，采用机器学习方法识别核心CuDEGs。我们分析了44个白塞病样本，以确定由这些核心CuDEGs衍生出的两个独特亚组。此外，我们进行了基因本体（GO）和京都基因与基因组百科全书通路富集研究，以及基因集富集分析（GSEA）和基因集变异分析（GSVA），并评估了免疫细胞浸润和免疫功能相关细胞。
共发现15个CuDEGs。使用机器学习算法，识别出6个核心CuDEGs： 、 、 、 、 和 。这些核心CuDEGs在白塞病样本中通常表现出较高的表达水平，从而确定了两个与CuDEGs相关的亚簇。亚簇2中大多数核心CuDEGs的表达较高。GSEA和GSVA结果表明，不同的核心CuDEGs在不同的通路中富集。免疫浸润和功能相关细胞的分析表明，核心CuDEGs参与了各种免疫反应过程，如巨噬细胞和中性粒细胞的激活，突出了核心CuDEGs之间免疫调节的显著差异。
本研究表明，CuDEGs在白塞病中差异表达，并与免疫活性和通路改变有关。这些发现表明，铜死亡可能通过调节免疫反应促进白塞病的进展。需要进一步的实验研究来证实这些基于生物信息学的发现，并探索其治疗潜力。
