通过生物信息学挖掘急性骨筋膜室综合征诊断和治疗的潜在靶点

Identifes potential targets for diagnosis and treatment of acute compartment syndrome through bioinformatics

目的:本研究旨在明确急性骨筋膜室综合征(ACS)关键基因模块及枢纽靶点。方法:将对照组和实验组大鼠趾长屈肌进行转录组测序,通过生物信息学的方法确定差异表达基因(DEGs),利用DEGs构建蛋白质互作网络(PPI)和关键基因模块找出Hub基因,再对核心基因集进行功能富集分析,最后对Hub基因进行验证。结果:通过5个正常大鼠和5个ACS大鼠趾长屈肌的转录组测序,确定了548个DEGs。将548个DEGs上传到String并用Cytoscape进行分析,挑选397个DEGs用于构建PPI。应用分子复合物检测(MCODE)对重要的基因模块进行聚类得到由27个基因组成的关键模块,Friends分析提示MyD88在这些基因中具有最重要的地位。通过对MCODE鉴定的核心基因集进行富集分析,发现核心基因集高度富集在炎症反应相关的生物学过程(BP)[如炎症反应、白细胞迁移的正向调节、对白介素-1(IL-1)的反应等]和京都基因与基因组百科全书(KEGG)(如TNF信号通路、NF-κB信号通路等)。结论:ACS伴随着明显的炎症反应,通过筛选药物抑制髓样分化因子(MyD88)或Toll样受体(TLR)/MyD88/核因子(NF-κB)信号通路减轻炎症反应可能对ACS的治疗具有一定效果,MyD88也为诊断ACS提供了一个可能的候选标志物。为ACS的发病机制提供新的见解,并为寻找新的诊断和治疗方法提供潜在的分子靶点。

Objective This study aimed to identify key gene modules and hub targets in acute compartment syndrome(ACS).Methods Transcriptome sequencing was performed on theflexor digitorum longus of control and experimental rats and differentially expressed genes(DEGs)were identifed by bioinformatics methods.protein-protein interaction(PPI)network and key gene modules were constructed using DEGs to identify hub genes.Enrichment analysis was performed on the core gene set,and the hub genes were validated.Results We determined 548 DEGs by transcriptome sequencing of theflexor digitorum longus of 5 normal rats and 5 ACS rats.The 548 DEGs were uploaded to String and analyzed using Cytoscape,and 397 DEGs were selected to construct PPI network.molecular complex detection(MCODE)was used to cluster important gene modules to obtain a key module composed of 27 genes,and friends analysis demonstrated that myeloid differentiation factor88(MyD88)had the most important position in these genes.Through enrichment analysis of the core gene set identifed by MCODE,we found that the core gene set was highly enriched in biological process(BP)related to the inflammatory response(such as inflammatory response,positive regulation of leukocyte migration,and response to interleukin 1)and Kyoto Encyclopedia of Genes and Genomes(KEGG)(such as TNF signaling pathway,NF-κB signaling pathway,etc.).Conclusion ACS is accompanied by a signifcant inflammatory response,and screening drugs to inhibit MyD88 or TLR/MyD88/NF-κB signaling pathway to reduce inflammation may have a certain effect on the treatment of ACS.MyD88 also provides a possible candidate biomarker for the diagnosis of ACS.Our study provides new insights into the pathogenesis of ACS and potential molecular targets for fnding new diagnostic and treatment methods.