"Extracellular vesicle-based biomarkers in diffuse large B-cell lymphoma: A systematic review and meta-analysis"

Diffuse large B-cell lymphoma (DLBCL) is a clinically and biologically heterogeneous malignancy. While current diagnostic and prognostic methods-such as histopathology, molecular subtyping, and imaging-remain essential to patient assessment, they face certain limitations. Thus, there is growing interest in complementary approaches such as extracellular vesicles (EVs), which may provide real-time, non-invasive insights into disease biology.

A systematic review and meta-analysis were conducted to evaluate the diagnostic and prognostic value of EVs in DLBCL. Databases including PubMed, Scopus, Web of Science, and Embase were searched. Pooled sensitivity, specificity, diagnostic odds ratio, and area under the curve were calculated for diagnostic studies. Prognostic outcomes were synthesized using hazard ratios for overall survival and event-free survival. Risk of bias was assessed using QUIPS and QUADAS-2 tools, and subgroup/sensitivity analyses and publication bias assessment were performed.

Pooled diagnostic performance of EVs showed high sensitivity (0.93), acceptable specificity (0.70), and an AUC of 0.89. Plasma-based EVs yielded superior accuracy (AUC = 0.94; DOR = 209). For prognosis, elevated EV levels were associated with significantly worse OS (HR = 6.21) and EFS (HR = 2.93). Subgroup analysis revealed reduced heterogeneity in high-quality studies, and sensitivity confirmed robustness. No major publication bias was detected.

EVs demonstrate substantial potential as reliable, non-invasive biomarkers for both the diagnosis and prognosis of DLBCL. Their integration into clinical workflows may enhance early detection, risk stratification, and disease monitoring. Future large-scale, prospective studies with standardized EV protocols are warranted to facilitate their clinical translation.