Lactylation-related multigene signature in multiple myeloma: integrated prognostic stratification, immune landscape profiling, and therapeutic guidance.

Multiple myeloma (MM) is an incurable hematologic malignancy with high heterogeneity and poor prognosis. Lactylation, a novel post-translational modification, drives tumor progression and immune dysregulation, yet its prognostic value in MM remains uncharacterized. To explore the prognostic value of lactylation-related genes in multiple myeloma, our study aims to construct and validate a lactylation-related multigene signature, which can provide integrated prognostic stratification, immune landscape profiling, and therapeutic guidance for MM patients. This study integrated 1,417 MM patients (859 from the TCGA-MMRF training cohort; 558 from the GSE24080 validation cohort) and 121 normal controls. Differential expression identified lactylation-related genes, and a prognostic model was constructed via LASSO-Cox regression. The model was validated in an independent cohort and we assessed immune infiltration and drug sensitivity. We finally identified four lactylation-associated prognostic genes (SLC19A1, KIF23, TOP2A, and XK) and categorized the patients into high-risk/low-risk groups, which differed in survival rates (P < 0.0001). The model showed robust accuracy (3-year AUC = 0.764) and validation (P = 0.0018). Low-risk patients exhibited enhanced anti-tumor immunity (activated dendritic cells↑, CD8⁺ T cells↑) and heightened sensitivity to bortezomi/venetoclax, etc. We established the lactylation-derived gene signature for MM, providing a clinical tool for risk stratification, immune profiling, and personalized therapy.