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 hematologicalmalignancy characterized by heterogeneous clinical and pathophysiologicalfeatures, which significantly influence treatment responses and outcomes.The identification of biomarkers that can predict drug response and guidetreatment decisions are crucial to improve therapeutic efficacy and patientoutcomes.Objective: To investigate the role of microRNAs (miRNAs) derived frombone marrow (BM) and peripheral blood (PB) in predicting treatmentresponse and survival outcomes in newly diagnosed MM (ndMM) patientsundergoing first-line treatment with bortezomib, thalidomide, anddexamethasone.Methodology: This study included 20 ndMM patients who underwent BM and PB sampling at diagnosis. MiRNAs were isolated and profiled usingNext-Generation Sequencing (NGS), followed by validation of differentiallyexpressed miRNAs by quantitative real-time PCR (qPCR). Clinical andresponse data were collected to assess correlations between miRNA levels, clinical characteristics, and patient outcomes. In silico analysis wasperformed to explore the potential biological and functional role of theidentified miRNAs.Key Findings:1. NGS profiling revealed several miRNAs that were differentiallyexpressed between treatment-refractory and sensitive patients, as well asbetween PB and BM.2. Four miRNAs (miR-665, miR-483-5p, miR-143-3p, and miR-145-5p) wereselected for further validation by qPCR, which confirmed the differentialexpression of these miRNAs in treatment-refractory and sensitive patients.3. Elevated levels of miR-665 were significantly associated with treatmentrefractoriness, more aggressive disease characteristics, and poorerclinical outcomes, including reduced overall survival.4. MiR-665 levels were higher in PB than in BM, suggesting the potentialutility of liquid biopsies as a non-invasive tool for predicting drugresistance.Conclusion: Our preliminary findings suggest that miR-665 may serve as a novel biomarker for predicting treatment response and guiding treatmentdecisions in MM. The study highlights the potential of miRNAs in liquidbiopsies as a predictive tool of drug response in MM, which could pave theway for personalized treatment strategies and improved patient outcomes.Future research is needed to validate these results in larger cohorts andexplore the underlying mechanisms of miR-665 in MM pathogenesis and drug resistance.