Mendelian Randomization Combined with Experimental Validation Identifies Prognostic Genes LMNB1 and PLXNB2 in the Immune Response in Multiple Myeloma

Introduction: Immune regulatory genes, such as PLXNB2, play critical roles in the tumor microenvironment, yet their specific functions in Multiple Myeloma [MM] remain largely unclear. Methods: Transcriptomic and clinical data for MM were retrieved from the Gene Expression Omnibus (GEO) database and analyzed alongside immune regulation-related genes identified from previous Mendelian randomization analysis. Correlations between these genes and immune functions, clinical risk scores, and survival prognosis were evaluated. Virtual drug sensitivity screening was performed for MM immune-related prognostic risk genes. In vitro experiments, including cell cloning, Transwell assays, scratch tests, and ELISA, were conducted to validate findings. Results: PLXNB2 expression was positively correlated with improved MM prognosis, whereas LMNB1 expression showed a negative correlation. MM cell lines exhibited reduced PLXNB2 and increased LMNB1 expression. Overexpression of PLXNB2 and knockdown of LMNB1 significantly inhibited MM cell proliferation, invasion, and migration. Furthermore, these manipulations decreased PD1 and CTLA-4 expression, enhancing the cytotoxic activity of immune cells against MM cells. Discussion: Our findings highlight the potential immune regulatory functions of PLXNB2 and LMNB1 in MM progression. The interplay between these genes may influence immune evasion and tumor aggressiveness, providing insights into potential therapeutic targets. Conclusion: Reduced PLXNB2 expression may drive LMNB1 upregulation, suppress immune cell responses, and promote MM progression. These genes represent promising biomarkers and therapeutic targets for improving MM treatment strategies.