二硫化物下垂,由二硫键应激引发的新发现的细胞死亡,其在骨质疏松症(OP)发病机制中的潜在作用引起了人们的关注。尽管据报道硫化物相关蛋白可调节OP中骨代谢的平衡,二硫键下垂调节剂的确切参与仍然难以捉摸。在这里,利用GSE56815数据集,我们进行了一项分析,以描述OP中与二硫键下垂相关的诊断簇和免疫景观.随后,对从OP患者和对照组获得的椎体组织进行RNA测序(RNA-seq),以验证关键的二硫键下垂基因表达.我们的分析揭示了七种重要的二硫化物沉积调节剂,包括FLNA,ACTB,PRDX1,SLC7A11,NUBPL,OXSM,和RAC1,区分OP样品与对照。此外,采用随机森林模型,我们确定了四种诊断性双硫度调节因子,包括FLNA,SLC7A11,NUBPL,和RAC1可能预测OP风险。使用GSE35956数据集构建并验证了集成这四个调节器的列线图模型,在临床决策中显示出有希望的效用,正如决策曲线分析所证实的那样。随后的一致性聚类分析使用显著的双硫度调节因子将OP样本分层为两个不同的双硫度调节子群(集群A和B)。B簇表现出较高的二硫键下垂评分,并暗示单核细胞免疫,与破骨细胞生成密切相关。值得注意的是,RNA-seq分析证实了两种二硫键沉积调节剂的表达模式,PRDX1和OXSM,与生物信息学预测一致。总的来说,我们的研究揭示了二硫化物沉积模式,为未来的OP管理提供潜在的标志物和免疫治疗途径。
Disulfidptosis, a newly recognized cell death triggered by disulfide stress, has garnered attention for its potential role in osteoporosis (OP) pathogenesis. Although sulfide-related proteins are reported to regulate the balance of bone metabolism in OP, the precise involvement of disulfidptosis regulators remains elusive. Herein, leveraging the GSE56815 dataset, we conducted an analysis to delineate disulfidptosis-associated diagnostic clusters and immune landscapes in OP. Subsequently, vertebral bone tissues obtained from OP patients and controls were subjected to RNA sequencing (RNA-seq) for the validation of key disulfidptosis gene expression. Our analysis unveiled seven significant disulfidptosis regulators, including FLNA, ACTB, PRDX1, SLC7A11, NUBPL, OXSM, and RAC1, distinguishing OP samples from controls. Furthermore, employing a random forest model, we identified four diagnostic disulfidptosis regulators including FLNA, SLC7A11, NUBPL, and RAC1 potentially predictive of OP risk. A nomogram model integrating these four regulators was constructed and validated using the GSE35956 dataset, demonstrating promising utility in clinical decision-making, as affirmed by decision curve analysis. Subsequent consensus clustering analysis stratified OP samples into two different disulfidptosis subgroups (clusters A and B) using significant disulfidptosis regulators, with cluster B exhibiting higher disulfidptosis scores and implicating monocyte immunity, closely linked to osteoclastogenesis. Notably, RNA-seq analysis corroborated the expression patterns of two disulfidptosis modulators, PRDX1 and OXSM, consistent with bioinformatics predictions. Collectively, our study sheds light on disulfidptosis patterns, offering potential markers and immunotherapeutic avenues for future OP management.