背景:骨关节炎(OA)是一种致残且非常普遍的疾病,影响全球数百万人。最近发现,二硫沉积是由胱氨酸过度积累诱导的一种新形式的细胞死亡。尽管意义重大,目前尚缺乏对OA中的二硫键凋亡相关基因(DRGs)的系统探索.
方法:本研究利用了三个与OA相关的数据集和DRG。通过将来自GSE114007的差异表达基因(DEGs)与DRGs相交,得到差异表达(DE)-DRGs。特征基因通过三种机器学习算法进行筛选。使用接受者工作特征曲线鉴定高诊断价值基因。通过表达验证确认了Hub基因。然后使用这些hub基因来构建列线图并进行富集,免疫,和相关分析。通过体外细胞实验进行hub基因的额外验证。
结果:SLC3A2和PDLIM1被指定为hub基因,显示卓越的诊断性能。PDLIM1在早期软骨细胞分化中呈低表达,后期明显上升,而SLC3A2显示出高的整体表达,在分化后期下降。细胞实验证实了SLC3A2和PDLIM1与软骨细胞炎症的相关性。
结论:两个hub基因,SLC3A2和PDLIM1被鉴定为与二硫化物沉积有关,为诊断和治疗OA提供潜在的方向。
BACKGROUND: Osteoarthritis (OA) is a disabling and highly prevalent condition affecting millions worldwide. Recently discovered, disulfidptosis represents a novel form of cell death induced by the excessive accumulation of cystine. Despite its significance, a systematic exploration of disulfidptosis-related genes (DRGs) in OA is lacking.
METHODS: This study utilized three OA-related datasets and DRGs. Differentially expressed (DE)-DRGs were derived by intersecting the differentially expressed genes (DEGs) from GSE114007 with DRGs. Feature genes underwent screening through three machine learning algorithms. High diagnostic value genes were identified using the receiver operating characteristic curve. Hub genes were confirmed through expression validation. These hub genes were then employed to construct a nomogram and conduct enrichment, immune, and correlation analyses. An additional validation of hub genes was performed through in vitro cell experiments.
RESULTS: SLC3A2 and PDLIM1 were designated as hub genes, displaying excellent diagnostic performance. PDLIM1 exhibited low expression in early chondrocyte differentiation, rising significantly in the late stage, while SLC3A2 showed high overall expression, declining in the late differentiation stage. Cellular experiments corroborated the correlation of SLC3A2 and PDLIM1 with chondrocyte inflammation.
CONCLUSIONS: Two hub genes, SLC3A2 and PDLIM1, were identified in relation to disulfidptosis, providing potential directions for diagnosing and treating OA.