Exploring the Role of Extracellular Vesicles in the Pathogenesis of Tuberculosis

TL;DR

This study explores how extracellular vesicles contribute to tuberculosis and identifies genes that could serve as biomarkers for diagnosis and treatment.

Contribution

The study identifies nine EV-related genes as potential biomarkers for TB, with VAMP5 showing high diagnostic accuracy.

Findings

Nine EV-related genes were found to be upregulated in TB patients compared to healthy controls.

VAMP5 demonstrated excellent diagnostic performance with high sensitivity and specificity.

EV-related genes are involved in exocytosis and immune response regulation in TB.

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.

Figures