Transcriptomics combined with in vitro experimental validation probes polyamine metabolic profiles in low-grade gliomas.

BACKGROUND

Polyamine metabolism supports the growth of myeloid-derived suppressor cells (MDSCs) in gliomas and is involved in developing an immunosuppressive state. However, the molecular patterns and prognostic features in low-grade gliomas (LGG) have not been adequately studied. This study was dedicated to exploring core targets of polyamine metabolism in LGG.

METHODS

A univariate Cox regression was employed to filter for genes correlated with overall survival (OS), and polyamine metabolism-related genes were identified into two distinct clusters by a consensus clustering algorithm, with significant differences in prognostic outcomes and levels of immune cell infiltration between metabolic subtypes. We then constructed prognostic models by least absolute shrinkage and selection operator (LASSO) and stepwise multivariate Cox regression. Next, differences in pathway enrichment, immune immersion and drug sensitivity were explored across risk subgroups. Finally, the role of the key gene spermine synthase (SMS) in LGG progression was explored by in vitro experiments.

RESULTS

We identified molecular subtypes of LGG linked to polyamine metabolism and demonstrated that risk scores validly forecasted patient prognosis and treatment response. SMS was a critical ingredient, and in vitro knockdown of SMS had been shown to suppress glioma cell proliferation, migration, and invasion, as well as cell cycle progression.

CONCLUSIONS

This study elucidates the underlying mechanisms of the molecular regulation of polyamine metabolism and its value for the clinical prognosis of LGG, with the key gene SMS playing a significant role in promoting the malignant progression of glioma cells.