Wu Haiyang, Wu Junhao, Wen Guowei
Shanghai Second People's Hospital, Shanghai, China.
Front Physiol. 2025 Sep 4;16:1605473. doi: 10.3389/fphys.2025.1605473. eCollection 2025.
Cuproptosis, a copper-dependent form of cell death, has been implicated in immune function and osteoporosis. However, the specific roles of cuproptosis-related genes (CRGs) in osteoporosis remain unclear. The differentially expressed CRGs from the Gene Expression Omnibus datasets of persons with osteoporosis and healthy individuals were categorized using R software tools in this study. Following that, the CIBERSORT algorithm and the GSVA technique were used to investigate the relationships between the different clusters and immune infiltration characteristics. Based on four machine learning techniques (Random Forest, Support Vector Machine, XGBoost, and Generalized Linear Model), Support Vector Machine and WGCNA analysis was carried out to identify the main genes linked to cuproptosis in the pathological course of osteoporosis. Subsequently, a model was built using the core genes related to cuproptosis to forecast the disease and identify potential treatment targets. The model was validated using an external dataset. In the end, a nomogram and calibration curve were created to improve this model's clinical applicability. Additionally, to investigate the possible biological roles of the core genes related to cuproptosis, we enriched them along several pathways. This study represents the first identification of key CRGs and core genes associated with cuproptosis in osteoporosis patients, findings that will facilitate the development of novel therapeutic strategies.
铜死亡是一种依赖铜的细胞死亡形式,与免疫功能和骨质疏松症有关。然而,铜死亡相关基因(CRGs)在骨质疏松症中的具体作用仍不清楚。本研究使用R软件工具对骨质疏松症患者和健康个体的基因表达综合数据集里差异表达的CRGs进行分类。随后,使用CIBERSORT算法和GSVA技术研究不同聚类与免疫浸润特征之间的关系。基于四种机器学习技术(随机森林、支持向量机、XGBoost和广义线性模型),进行支持向量机和加权基因共表达网络分析(WGCNA),以确定在骨质疏松症病理过程中与铜死亡相关的主要基因。随后,使用与铜死亡相关的核心基因建立模型,以预测疾病并确定潜在的治疗靶点。该模型使用外部数据集进行验证。最后,创建了列线图和校准曲线,以提高该模型的临床适用性。此外,为了研究与铜死亡相关的核心基因可能的生物学作用,我们沿着几条通路对它们进行了富集分析。本研究首次鉴定了骨质疏松症患者中与铜死亡相关的关键CRGs和核心基因,这些发现将有助于开发新的治疗策略。