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Abstract：
Tuberculosis (TB) remains a significant global health concern, necessitating accurate diagnosis and treatment monitoring. Extracellular vesicles (EVs), including exosomes, play crucial roles in disease progression, with their associated genes serving as potential biomarkers and therapeutic targets. Leveraging publicly available RNA-Seq datasets of TB patients and healthy controls (HCs), to identify differentially expressed genes (DEGs) and their associated protein-protein interaction networks and immune cell profiles, the common EV-related DEGs were identified and validated in the GSE42830 and GSE40553 datasets. We have identified nine common EV-related DEGs (SERPINA1, TNFAIP6, MAPK14, STAT1, ITGA2B, VAMP5, CTSL, CEACAM1, and PLAUR) upregulated in TB patients. Immune cell infiltration analysis revealed significant differences between TB patients and HCs, highlighting increased proportions of various immune cells in TB patients. These DEGs are involved in crucial cellular processes and pathways related to exocytosis and immune response regulation. Notably, VAMP5 exhibited excellent diagnostic performance (AUC-0.993, sensitivity-93.8%, specificity-100%), with potential as a novel biomarker for TB. The EV-related genes can serve as novel potential biomarkers that can distinguish between TB and HCs. VAMP5, which functions in exosome biogenesis and showed significant upregulation in TB, can be targeted for therapeutic interventions and treatment outcomes.
摘要：
结核病（TB）仍然是一个重要的全球健康问题，需要准确的诊断和治疗监测。细胞外囊泡（EV），包括外泌体，在疾病进展中发挥关键作用，与它们相关的基因作为潜在的生物标志物和治疗靶标。利用公开可用的结核病患者和健康对照（HC）的RNA-Seq数据集，鉴定差异表达基因（DEGs）及其相关的蛋白质-蛋白质相互作用网络和免疫细胞谱，在GSE42830和GSE40553数据集中鉴定并验证了常见的EV相关DEG.WehaveidentifiedninecommonEV-relatedDEG(SERPINA1,TNFAIP6,MAPK14,STAT1,ITGA2B,VAMP5,CTSL,CEACAM1和PLAUR）在结核病患者中上调。免疫细胞浸润分析显示，TB患者和HCs之间存在显着差异，强调结核病患者中各种免疫细胞比例的增加。这些DEGs参与与胞吐和免疫应答调节相关的关键细胞过程和途径。值得注意的是,VAMP5表现出出色的诊断性能（AUC-0.993，灵敏度-93.8％，特异性-100%)，作为结核病的新型生物标志物的潜力。EV相关基因可以作为新的潜在生物标志物，可以区分TB和HC。VAMP5在外泌体生物发生中起作用，并在TB中显示出显着的上调，可以有针对性地进行治疗干预和治疗结果。
