Identification of plasma exosome circRNA as potential novel biomarkers for DLBCL and circrna-miRNA-mRNA network analysis.

[UNLABELLED] Diffuse large B-cell lymphoma (DLBCL), the most common aggressive non-Hodgkin lymphoma, urgently requires novel biomarkers for clinical diagnosis and therapeutic monitoring. Plasma exosomes from three DLBCL patients and three healthy controls were isolated via ultracentrifugation, and differentially expressed circular RNAs (circRNAs) were screened using Arraystar V2 microarrays (fold change [FC] ≥ 1.2,  ≤ 0.05). Candidate circRNAs were validated by quantitative real-time PCR (qRT-PCR) in 55 DLBCL patients and 25 controls. Microarray analysis identified 269 dysregulated circRNAs (152 upregulated, 117 downregulated; FC ≥ 1.2,  ≤ 0.05). RT-qPCR confirmed significantly elevated expression of hsa_circ_400230, hsa_circ_001393, and hsa_circ_404447 in DLBCL ( < 0.05), with areas under the ROC curve (AUCs) of 0.7622, 0.7244, and 0.6618, respectively. High hsa_circ_001393 expression correlated with advanced age (> 60 years), stage III/IV, high International Prognostic Index (IPI 3–5), elevated β2-microglobulin (> 2 mg/L), and non-complete remission (Non-CR) status ( < 0.05). Combined detection with lactate dehydrogenase (LDH) improved predictive efficacy (AUC = 0.817,  = 0.002). Post-chemotherapy complete remission (CR) patients exhibited significant reduction in hsa_circ_001393 ( = 0.0174). Competing endogenous RNA (ceRNA) network analysis identified MLLT3 as a hub gene, with overexpression associated with shorter survival (hazard ratio [HR] = 2.31,  = 0.0042). These findings demonstrate that Plasma exosomal hsa_circ_400230/001393/404,447 are novel diagnostic biomarkers. hsa_circ_001393 predicts therapeutic resistance and dynamically reflects chemotherapy response, potentially via the hsa-miR-1290/MLLT3 axis. This study advances liquid biopsy strategies for DLBCL management.

[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1007/s10238-025-02019-w.