原发性颞下颌关节色素沉着绒毛结节性滑膜炎的潜在诊断标志物预测研究

Predictive study regarding potential diagnostic markers in primary pigmented villonodular synovitis of temporomandibular joint

目的:根据生物信息学分析确定颞下颌关节(TMJ)色素沉着绒毛结节性滑膜炎(PVNS)患者相关潜在诊断标志物,并评估TMJ PVNS在疾病发生发展中的作用。方法:根据基因芯片(GSE3698)原始矩阵数据在探针水平分析基因表达谱。使用R语言编程分析并可视化结果。筛查TMJ PVNS差异表达基因(DEGs),对细胞群体进行功能注释和信号通路富集分析。基于STRING数据库构建蛋白质互作(PPI)网络。绘制集成受试者工作特征曲线确定TMJ PVNS诊断标志物。使用CIBERSORT软件从测序数据对TMJ PVNS中免疫细胞亚型进行定量分析,并评估诊断标志物与浸润免疫细胞之间的相关性。结果:共计筛选139个DEGs,包括46个下调基因和93个上调基因。功能富集分析显示,共计44个生物过程、30个细胞成分、18个分子功能和22条信号通路具有统计学意义。通过PPI网络筛选出8个表达显著上调的Hub基因,其中FCER1G、HLA-DPB1、LAPTM5和TYROBP被鉴定为TMJ PVNS的潜在诊断生物标志物。免疫细胞浸润分析表明,中性粒细胞及M2型巨噬细胞与TMJ PVNS的发生发展有关。此外,对筛查出的诊断标志物和浸润免疫细胞亚群的相关性分析发现,FCER1G、LAPTM5、TYROBP与浆细胞浸润呈负相关;而FCER1G、HLA-DPB1、LAPTM5、TYROBP则与M2型巨噬细胞和中性粒细胞浸润呈正相关。结论:FCER1G、HLA-DPB1、LAPTM5和TYROBP可作为TMJ PVNS的潜在诊断标志物,免疫细胞浸润在该罕见病的发生和发展中起着重要作用。

Objective:To identify potential diagnostic markers and assess their role in the pathogenesis and progress of temporoman⁃dibular joint(TMJ)pigmented villous nodular synovitis(PVNS)based on bioinformatics analysis.Methods:The gene expression pro⁃file was analyzed at the probe level according to the raw matrix data of gene chip(GSE3698).R language programming was used to an⁃alyze and visualize the results.DEGs were screened in TMJ PVNS.The functional annotation and signal pathway enrichment analysis on these cell populations.PPI network was established based on the STRING database.Summary receiver operating characteristic curves were plotted to determine diagnostic biomarkers of TMJ PVNS.Quantitative analysis of immune cell subtypes in TMJ PVNS was calcu⁃lated using CIBERSORT software from sequences and the association between diagnostic markers and infiltrating immune cells was also estimated accordingly.Results:Totally 139 DEGs were found out including 46 downregulated and 93 upregulated genes.Functional en⁃richment analysis revealed that 44 biological process,30 cellular component,18 molecular function,and 22 signal pathways were sta⁃tistically significant.Eight hub genes with significantly upregulated expression were screened by PPI network.FCER1G,HLA⁃DPB1,LAPTM5,and TYROBP were identified as potential diagnostic biomarkers for TMJ PVNS.Immunocyte infiltration analysis showed neutrophils and M2 macrophages were associated with the pathogenesis and progress of TMJ PVNS.In addition,the correlation analysis con⁃cerning the identified diagnostic markers and infiltrating immune cell subpopulations indicated that FCER1G,LAPTM5,TYROBP were negatively related to plasma cell infiltration;FCER1G,HLA⁃DPB1,LAPTM5,and TYROBP were positively related to M2 macrophage infiltration and that neutrophils.Conclusions:This investigation concluded that FCER1G,HLA⁃DPB1,LAPTM5,and TYROBP as potential diagnostic markers and immune cell infiltration played an important role in the pathogenesis and progress of TMJ PVNS.