MicroRNA-665 and its potential role in drug response and survival outcomes in Multiple Myeloma: a preliminary study. MicroRNA-665 and its potential role in drug response and survival outcomes in Multiple Myeloma: a preliminary study

Background: Multiple myeloma (MM) is a complex hematological malignancy characterized by heterogeneous clinical and pathophysiological features, which significantly influence treatment responses and outcomes. The identification of biomarkers that can predict drug response and guide treatment decisions are crucial to improve therapeutic efficacy and patient outcomes. Objective: To investigate the role of microRNAs (miRNAs) derived from bone marrow (BM) and peripheral blood (PB) in predicting treatment response and survival outcomes in newly diagnosed MM (ndMM) patients undergoing first-line treatment with bortezomib, thalidomide, and dexamethasone. Methodology: This study included 20 ndMM patients who underwent BM and PB sampling at diagnosis. MiRNAs were isolated and profiled using Next-Generation Sequencing (NGS), followed by validation of differentially expressed miRNAs by quantitative real-time PCR (qPCR). Clinical and response data were collected to assess correlations between miRNA levels, clinical characteristics, and patient outcomes. In silico analysis was performed to explore the potential biological and functional role of the identified miRNAs. Key Findings: 1. NGS profiling revealed several miRNAs that were differentially expressed between treatment-refractory and sensitive patients, as well as between PB and BM. 2. Four miRNAs (miR-665, miR-483-5p, miR-143-3p, and miR-145-5p) were selected for further validation by qPCR, which confirmed the differential expression of these miRNAs in treatment-refractory and sensitive patients. 3. Elevated levels of miR-665 were significantly associated with treatment refractoriness, more aggressive disease characteristics, and poorer clinical outcomes, including reduced overall survival. 4. MiR-665 levels were higher in PB than in BM, suggesting the potential utility of liquid biopsies as a non-invasive tool for predicting drug resistance. Conclusion: Our preliminary findings suggest that miR-665 may serve as a novel biomarker for predicting treatment response and guiding treatment decisions in MM. The study highlights the potential of miRNAs in liquid biopsies as a predictive tool of drug response in MM, which could pave the way for personalized treatment strategies and improved patient outcomes. Future research is needed to validate these results in larger cohorts and explore the underlying mechanisms of miR-665 in MM pathogenesis and drug resistance.