miR-193-5p, miR-1307-5p, and miR-671-5p: Potential biomarkers for chemoresistance in diffuse large B-cell lymphoma.

Background and objectives Diffuse large B-cell lymphoma presents a significant challenge due to its high rate of treatment failure in 40% of patients. In this study we screened microRNAs as biomarkers in chemotherapy non-responding patients, to allow their early prognostication. Methods In the exploratory phase, whole transcriptome microRNA profiling was conducted on 10 diffuse large B-cell lymphoma cases. Three patients achieved complete remission, while seven had refractory or relapsed disease. The differentially expressed miRNAs were validated in 41 retrospective, treatment-naive diffuse large B-cell lymphoma biopsies, including the original 10 cases. Additionally, 33 cases with paired biopsy and plasma samples were prospectively evaluated using qRT-PCR to correlate miRNA expression with clinical outcomes. Functional validation to identify downstream pathways was done by knocking down identified miRNAs in JM-1 cells by semi-quantitative proteomics. Results miR-193b-5p, miR-1307-5p, and miR-671-5p expression were downregulated in refractory/relapsed diffuse large B-cell lymphoma biopsies. Plasma miRNA levels did not reflect prognosis. In vitro proteomics showed their impact on key oncogenic pathways, revealing significant enrichment of replication and transcription-related proteins. Interpretation and conclusions The expression of miR-193b-5p, miR-1307-5p, and miR-671-5p miRNAs in diffuse large B-cell lymphoma tissues may serve as predictive biomarkers.