First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, Guangdong, China.
Sci Rep. 2024 Nov 9;14(1):27336. doi: 10.1038/s41598-024-78392-5.
Atherosclerosis (AS) is the leading cause of coronary heart disease, which is the primary cause of death worldwide. Recent studies have identified disulfidptosis as a new type of cell death that may be involved in onset and development of many diseases. However, the role of disulfidptosis in AS is not clear. In this study, bioinformatics analysis and experiments in vivo and in vitro were performed to evaluate the potential relationship between disulfidptosis and AS. AS-related sequencing data were obtained from the Gene Expression Omnibus (GEO). Bioinformatics techniques were used to evaluate differentially expressed genes (DEGs) associated with disulfidptosis-related AS. Hub genes were screened using least absolute shrinkage and selection operator (LASSO) and random forests (RF) methods. In addition, we established a foam cell model in vitro and an AS mouse model in vivo to verify the expressions of hub genes. In addition, we constructed a diagnostic nomogram with hub genes to predict progression of AS. Finally, the consensus clustering method was used to establish two different subtypes, and associations between subtypes and immunity were explored. As the results, 9 disulfidptosis-related AS DEGs were identified from GSE28829 and GSE43292 datasets. Evaluation of DEGs using LASSO and RF methods resulted in identification of 4 hub genes (CAPZB, DSTN, MYL6, PDLIM1), which were analyzed for diagnostic value using ROC curve analysis and verified in vitro and in vivo. Furthermore, a nomogram including hub genes was established that accurately predicted the occurrence of AS. The consensus clustering algorithm was used to separate patients with early atherosclerotic plaques and patients with advanced atherosclerotic plaques into two disulfidptosis subtypes. Cluster B displayed higher levels of infiltrating immune cells, which indicated that patients in cluster B may have a positive immune response for progression of AS. In summary, disulfidptosis-related genes including CAPZB, DSTN, MYL6, and PDLIM1 may be diagnostic markers and therapeutic targets for AS. In addition, these genes are closely related to immune cells, which may inform immunotherapy for AS.
动脉粥样硬化（AS）是冠心病的主要病因，也是全球首要致死原因。最近的研究发现，二硫键细胞凋亡是一种新的细胞死亡方式，可能与许多疾病的发生和发展有关。然而，二硫键细胞凋亡在 AS 中的作用尚不清楚。本研究通过生物信息学分析及体内、体外实验，评估二硫键细胞凋亡与 AS 之间的潜在关系。从基因表达综合数据库（GEO）中获得与 AS 相关的测序数据。采用生物信息学技术评估与二硫键细胞凋亡相关的 AS 差异表达基因（DEGs）。采用最小绝对收缩和选择算子（LASSO）和随机森林（RF）方法筛选枢纽基因。此外，我们在体外建立泡沫细胞模型，在体内建立 AS 小鼠模型，验证枢纽基因的表达。此外，我们构建了一个包含枢纽基因的诊断列线图来预测 AS 的进展。最后，采用共识聚类方法建立了两种不同的亚型，并探讨了亚型与免疫之间的关系。结果从 GSE28829 和 GSE43292 数据集鉴定了 9 个与二硫键细胞凋亡相关的 AS DEGs。采用 LASSO 和 RF 方法评估 DEGs，鉴定出 4 个枢纽基因（CAPZB、DSTN、MYL6、PDLIM1），并通过 ROC 曲线分析评估其诊断价值，并在体内外进行验证。此外，还建立了一个包含枢纽基因的列线图，该列线图能准确预测 AS 的发生。采用共识聚类算法将早期动脉粥样硬化斑块患者和晚期动脉粥样硬化斑块患者分为二硫键细胞凋亡两种亚型。B 型簇显示浸润免疫细胞水平较高，表明 B 型簇患者可能对 AS 的进展有积极的免疫反应。总之，包括 CAPZB、DSTN、MYL6 和 PDLIM1 在内的与二硫键细胞凋亡相关的基因可能是 AS 的诊断标志物和治疗靶点。此外，这些基因与免疫细胞密切相关，这可能为 AS 的免疫治疗提供信息。
