Integrated analysis of bulk and single-cell RNA sequencing reveals the impact of nicotinamide and tryptophan metabolism on glioma prognosis and immunotherapy sensitivity

BMC Neurol. 2024 Oct 28;24(1):419. doi: 10.1186/s12883-024-03924-5.

Abstract

Background: Nicotinamide and tryptophan metabolism play important roles in regulating tumor synthesis metabolism and signal transduction functions. However, their comprehensive impact on the prognosis and the tumor immune microenvironment of glioma is still unclear. The purpose of this study was to investigate the association of nicotinamide and tryptophan metabolism with prognosis and immune status of gliomas and to develop relevant models for predicting prognosis and sensitivity to immunotherapy in gliomas.

Methods: Bulk and single-cell transcriptome data from TCGA, CGGA and GSE159416 were obtained for this study. Gliomas were classified based on nicotinamide and tryptophan metabolism, and PPI network associated with differentially expressed genes was established. The core genes were identified and the risk model was established by machine learning techniques, including univariate Cox regression and LASSO regression. Then the risk model was validated with data from the CGGA. Finally, the effects of genes in the risk model on the biological behavior of gliomas were verified by in vitro experiments.

Results: The high nicotinamide and tryptophan metabolism is associated with poor prognosis and high levels of immune cell infiltration in glioma. Seven of the core genes related to nicotinamide and tryptophan metabolism were used to construct a risk model, and the model has good predictive ability for prognosis, immune microenvironment, and response to immune checkpoint therapy of glioma. We also confirmed that high expression of TGFBI can lead to an increased level of migration, invasion, and EMT of glioma cells, and the aforementioned effect of TGFBI can be reduced by FAK inhibitor PF-573,228.

Conclusions: Our study evaluated the effects of nicotinamide and tryptophan metabolism on the prognosis and tumor immune microenvironment of glioma, which can help predict the prognosis and sensitivity to immunotherapy of glioma.

Keywords: Core genes; Glioma; Immunotherapy sensitivity; Nicotinamide metabolism; Prognosis; Tryptophan metabolism.

MeSH terms

  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / immunology
  • Brain Neoplasms* / metabolism
  • Glioma* / drug therapy
  • Glioma* / genetics
  • Glioma* / immunology
  • Glioma* / metabolism
  • Humans
  • Immunotherapy* / methods
  • Niacinamide* / therapeutic use
  • Prognosis
  • Sequence Analysis, RNA / methods
  • Single-Cell Analysis / methods
  • Tryptophan* / metabolism
  • Tumor Microenvironment* / drug effects
  • Tumor Microenvironment* / immunology

Substances

  • Tryptophan
  • Niacinamide