A novel risk score model of lactate metabolism for predicting outcomes and immune signatures in acute myeloid leukemia

Sci Rep. 2024 Oct 28;14(1):25742. doi: 10.1038/s41598-024-76919-4.

Abstract

Acute myeloid leukemia (AML) is a malignant tumor with high recurrence and refractory rates and low survival rates. Increased glycolysis is characteristic of metabolism in AML blast cells and is also associated with chemotherapy resistance. The purpose of this study was to use gene expression and clinical information from The Cancer Genome Atlas (TCGA) database to identify subtypes of AML associated with lactate metabolism. Two different subtypes linked to lactate metabolism, each with specific immunological features and consequences for prognosis, were identified in this study. Using the TCGA and International Cancer Genome Consortium (GEO) cohorts, a prognostic model composed of genes (LMNA, RETN and HK1) for the prognostic value of the lactate metabolism-related risk score prognostic model was created and validated, suggesting possible therapeutic uses. Additionally, the diagnostic value of the prognostic model genes was explored. LMNA and HK1 were ultimately identified as hub genes, and their roles in AML were determined through immune infiltration, GeneMANIA, GSEA, methylation analysis and single-cell analysis. LMNA was upregulated in AML associating with a poor prognosis while HK1 was downregulated in AML associating with a favorable prognosis. The findings underscore the noteworthy impact of genes linked to lactate metabolism in AML and illustrate the possible therapeutic usefulness of the lactate metabolism-related risk score and the hub lactate metabolism-related genes in guiding AML patients' treatment choices.

Keywords: Acute myeloid leukemia; Immune signature; Lactate metabolism-associated gene; OS; Risk model.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Female
  • Gene Expression Regulation, Leukemic
  • Humans
  • Lactic Acid* / metabolism
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / immunology
  • Leukemia, Myeloid, Acute* / metabolism
  • Male
  • Middle Aged
  • Prognosis

Substances

  • Lactic Acid
  • Biomarkers, Tumor