泛凋亡因子在骨质疏松症中的诊断标记物及亚型分析

Molecular mechanism of PANoptosis in diagnostic markers and subtyping of osteoporosis

背景:研究推测泛凋亡可能参与了骨质疏松的病理过程,但目前尚未有泛凋亡基因在骨质疏松中的相关机制研究。目的:分析泛凋亡调节因子在骨质疏松症发生发展过程中的生物学机制。方法:从Gene Expresion omnibus(GEO)数据库中获得GSE56815数据集,提取泛凋亡基因进行差异分析。通过随机森林树模型筛选泛凋亡关键基因,构建疾病风险预测模型。运用共识聚类算法、单样本基因组富集分析以及免疫浸润分析探讨不同泛凋亡分子亚型间的差异性。通过医学本体信息检索平台Coremine medical数据库预测调节泛凋亡关键基因的中药药物。结果与结论:①基于4个泛凋亡关键基因(CASP1、CASP10、MEFV、TNF),确定了骨质疏松症中的诊断标志物,构建了患病风险预测模型并进行验证;②将骨质疏松患者分为2种不同的泛凋亡亚型(簇A、B和基因簇A、B),且簇B和基因簇B的泛凋亡评分分别高于簇A和基因簇A;③通过Coremine medical数据库预测出人参等能调节泛凋亡关键基因的中药药物。

BACKGROUND:It has been hypothesized that PANoptosis may be involved in the pathologic process of osteoporosis,but there have been no studies addressing the mechanisms of PANoptosis genes in osteoporosis.OBJECTIVE:To analyze the biological mechanism of PANoptosis regulators in the occurrence and development of osteoporosis.METHODS:The GSE56815 dataset was obtained from the Gene Expression Omnibus database and PANoptosis genes were extracted for differential analysis.The key genes of PANoptosis were screened by random forest tree model to construct a disease risk prediction model.Consensus clustering algorithm,single sample genome enrichment analysis and immune infiltration analysis were used to explore the differences between different PANoptosis molecular subtypes.Herbal drugs that regulate the key genes of PANoptosis were predicted through Coremine medical database,a medical ontology information retrieval platform.RESULTS AND CONCLUSION:Based on the four PANoptosis key genes(CASP1,CASP10,MEFV,and TNF),the diagnostic markers of osteoporosis were determined,and the risk prediction model was constructed and verified.Osteoporosis was divided into two different PANoptosis subtypes(clusters A,B and gene clusters A,B),and the PANoptosis scores of cluster B and gene cluster B were higher than those of cluster A and gene cluster A,respectively.Traditional Chinese drugs such as ginseng which can regulate the key genes of PANoptosis were predicted by the Coremine medical database.