Cyclic cytokines mediated the effect of immune cells on meningioma: a two-step, mediation mendelian randomization study

BMC Cancer. 2025 Oct 23;25(1):1633. doi: 10.1186/s12885-025-14694-9.

Abstract

Background: Meningioma is a common central nervous system tumor that poses serious health hazards and increases with age. However, the role of immune cells in meningioma remains incompletely understood.

Methods: Data from genome-wide association studies on meningioma, cyclic cytokines, and immune cells were comprehensively analyzed. We conducted a two-step, two-sample mendelian randomization study to investigate the causal relationship between immune cell characteristics and meningioma. Furthermore, we examined the mediation effect of cyclic cytokines in connecting the association of immune cells with the risk of meningioma.

Results: Eighteen immune phenotypes showed significant correlations with meningioma risk. Notably, Naive CD4-CD8- T cell %T Cell (OR: 1.380, 95% CI: 1.013-1.880, P = 0.041) and FSC-A on Myeloid Dendritic Cell (OR: 1.177, 95% CI: 1.045-1.325, P = 0.007) were implicated in promoting meningioma via MMP-1. The mediation effects of MMP-1 in these two immune cells were 0.023 and 0.015, with corresponding proportions of 7.110% and 8.981% in the mediation effect ratio.

Conclusion: Our study elucidated the causal relationship between immune cell phenotypes and meningioma, pinpointing the potential role of MMP-1. These findings provide clues for potential therapeutic targets.

Keywords: Causal relationship; Cyclic cytokines; Immunophenotype; Mendelian randomization; Meningioma.

MeSH terms

  • Cytokines* / immunology
  • Cytokines* / metabolism
  • Dendritic Cells / immunology
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Mendelian Randomization Analysis
  • Meningeal Neoplasms* / genetics
  • Meningeal Neoplasms* / immunology
  • Meningioma* / genetics
  • Meningioma* / immunology
  • Meningioma* / pathology
  • Polymorphism, Single Nucleotide

Substances

  • Cytokines