Plasma-derived exosomal miRNA as a promising diagnostic biomarker for detection of diffuse large B-cell lymphoma.

[BACKGROUND] Diffuse large B-cell lymphoma (DLBCL) is a malignant tumor with moderate-high aggressiveness and heterogeneity. In recent years, several studies have shown that tumor cell-derived exosomes are involved in the process of tumorigenesis and progression through microRNA (miRNA). Therefore, exosomal miRNAs are potential diagnostic and prognostic biomarkers for cancer. The aim of this study was to explore the potential of a set of exosomal miRNAs in peripheral blood as noninvasive biomarkers for the auxiliary diagnosis of DLBCL.

[METHODS] Exosomes were collected from the peripheral blood of three DLBCL patients and two healthy controls, and miRNA expression was detected using high-throughput sequencing technology. MiRNAs were analyzed by Weighted Gene Co-expression Network Analysis to screen out the correlated model genes of DLBCL, subsequently, receiver operating characteristic (ROC) curves were constructed to verify the diagnostic efficacy of this group of miRNAs and validation was performed using the GSE171272 dataset. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for the target genes of hsa-miR-589-5p, hsa-miR-4728-3p and hsa-miR-5006-3p.

[RESULTS] We identified eight exosomal miRNAs with the potential to differentiate DLBCL patients from healthy controls. ROC curves were generated using the GSE171272 dataset to assess the diagnostic performance of these miRNAs. Among them, hsa-miR-589-5p, hsa-miR-4728-3p, hsa-miR-5006-3p, hsa-miR-30b-5p, hsa-miR-4323, hsa-miR-484, hsa-miR-4500, and hsa-miR-99a-5p exhibited an AUC greater than 0.8. Specifically, the area under the curve (AUC) of hsa-miR-589-5p, hsa-miR-4728-3p and hsa-miR-5006-3p were both 1.00 [95% confidence interval (CI): 0.93-1.00].

[CONCLUSIONS] In this study, exosomal miRNAs contribute to the diagnosis of DLBCL and may serve as non-invasive diagnostic biomarkers for DLBCL. This offers novel perspectives on utilizing exosomal miRNAs for the early identification of DLBCL and their potential clinical application. However, given the small size of the discovery cohort, these estimates are presented as exploratory and should be confirmed in larger independent cohorts.