The expression level of hsa-miR-146a-5p in plasma-derived exosomes of patients with diffuse large B-cell lymphoma.

Background: The standard treatment for patients with diffuse large B-cell lymphoma (DLBCL) had been rituximab-based immunochemotherapy. However, the biological and clinical heterogeneity within DLBCL seems to affect treatment outcome. Therefore, the evaluation of miRNA levels might be useful in predicting treatment response and relapse risk. miR-146a is a modulator of innate and acquired immunity and may play an important role in predicting treatment response. The aim of the present study was to compare the expression level of miR-146a in plasma-derived exosomes of responsive DLBCL patients (response to R-CHOP (Rituximab, and Cyclophosphamide, Hydroxydaunorubicin, Oncovine and Prednisone)), refractory DLBCL patients (resistant to R-CHOP), patients receiving R-CHOP, and healthy donors.

Materials and Methods: After the preparation of plasma and isolation of exosomes, the presence of plasma-derived exosome was confirmed by Zetaseizer, electron microscope, and Western blot. The patients' medical records were collected and analyzed. The expression level of exosomal miR-146a was evaluated in DLBCL patients and healthy donors using real-time polymerase chain reaction (PCR). The -ΔCt values of miR-146a were compared among responsive patients ( n = 17), refractory patients ( n = 16), patients receiving R-CHOP therapy ( n = 15), and healthy donors ( n = 6).

Results: The presence and size of plasma-derived exosomes were confirmed. Our findings did not show any significant difference in the expression level of exosomal miR-146a between DLBCL patients and healthy donors ( P = 0.48). As well, the clinical and histopathological parameters were not correlated with the expression level of exosomal miR-146a or plasma miR-146a. The expression level of plasma miR-146 was lower than the expression level of exosomal miR-146 ( P = 0.01).

Conclusion: Exosomal miR-146a might be useful as a promising "liquid biopsy" biomarker in predicting treatment response and relapse risk; however, we could not find significant differences due to small sample size.