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.