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<p>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 (<i>P</i> &lt; 0.0001). The model showed robust accuracy (3-year AUC = 0.764) and validation (<i>P</i> = 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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年11月8日

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  • Wuyang Zhang,
  • Shuai Ming,
  • Peng Cheng,
  • Dan Shi,
  • Jingyu Li,
  • Bin Wang,
  • Yu Fang,
  • Mengru Li,
  • Wei Cao,
  • Min Wang,
  • Zaibao Wang,
  • Jiawei Xiao,
  • Wei Wei

摘要

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.