骨质疏松诊断标志物的筛选及其与免疫浸润的关系

Screening of diagnostic biomarkers and their relations with immune cell infiltration in osteoporosis

目的寻找潜在的骨质疏松(OP)诊断标志物,并分析免疫浸润在OP发展中的作用。方法使用源自基因表达综合数据库(GEO)的基因表达谱数据集来鉴定OP的差异表达基因(DEGs),并通过富集分析揭示DEGs的潜在机制;采用最小绝对值收敛和选择算法(LASSO)逻辑回归分析和支持向量机递归特征剔除算法(SVM-RFE)筛选和验证OP的诊断标志物;使用CIBERSORT评价OP组织中免疫细胞的浸润情况,分析诊断标志物与免疫细胞浸润的相关性。结果本研究共筛选出5个诊断相关基因为关键基因:SKAP2、SLC30A3、TDRD12、RPL10和CSPP1。SKAP2、SLC30A3、TDRD12、RPL10和CSPP1被确定为OP的诊断标志物。SKAP2、SLC30A3、TDRD12、RPL10联合CSPP1诊断OP的效能较高。22种免疫细胞的相关热图显示,活化的肥大细胞与浆细胞呈正相关,静息肥大细胞与嗜酸性粒细胞呈正相关。此外,活化的CD4记忆T细胞与调节性T细胞呈负相关,巨噬细胞与记忆B细胞呈负相关。结论免疫细胞浸润在OP的发生和发展中至关重要,静息CD4记忆T细胞和M2巨噬细胞可能参与了OP的发病机制,这些结果有助于为OP的诊断和治疗提供新的思路。

Objective To search for potential diagnostic markers of osteoporosis(OP)and analyze the roles of immune infiltration in the development of OP.Methods Gene expression profile datasets derived from the Gene Expression Omnibus database(GEO)were first used to identify differentially expressed genes(DEGs)for OP.Then,the underlying mechanisms of DEGs were revealed by enrichment analysis.Least Absolute Shrinkage and Selection Operator(LASSO)Logistic regression and support vector machine recursive feature elimination algorithm(SVM-RFE)were used to screen and validate the diagnostic markers of OP.CIBERSORT was used to evaluate the infiltration of immune cells in OP tissues,and the correlations between the diagnostic markers and immune cell infiltration were detected.Results In this study,five diagnostic genes were selected as key genes:SKAP2,SLC30A3,TDRD12,RPL10 and CSPP1.SKAP2,SLC30A3,TDRD12,RPL10 and CSPP1 were identified as diagnostic markers of OP.SKAP2,SLC30A3,TDRD12 and RPL10 combined with CSPP1 had higher diagnostic efficiency.The heat maps of 22 kinds of immune cells showed that activated mast cells were positively correlated with plasma cells,and resting mast cells positively correlated with eosinophils.In addition,activated CD4 memory T cells were negatively correlated with regulatory T cells,and macrophages were negatively correlated with memory B cells.Conclusion Immune cell infiltration is crucial in the occurrence and development of OP.Resting CD4 memory T cells and M2 macrophages may be involved in the pathogenesis of osteoporosis.These results help to provide new ideas for the diagnosis and treatment of OP.