Peroxisomal fatty acid oxidation-related signature for predicting prognosis and therapeutic response in low-grade glioma.

INTRODUCTION: Metabolic reprogramming is one of the hallmarks of cancer. Increasing evidence indicates that lipid metabolism reprogramming plays an important role in the development of tumors, especially glioma. Fatty acid oxidation (FAO) occurs in both mitochondria and peroxisomes. At present, studies of FAO have mainly focused on mitochondria, while research on peroxisomes remains limited. METHODS: This study utilized bioinformatics methods and functional assays to explore the potential role of peroxisomal FAO in low-grade glioma (LGG). RESULTS: As a result, we constructed a reliable peroxisomal FAO-related prognostic model for LGG based on different combinations of 10 well-performing machine learning algorithms. Gene set enrichment analysis (GSEA) and drug sensitivity prediction analyses suggested that the identified prognostic peroxisomal FAO-related genes may contribute to therapeutic resistance in LGG. Functional assays further demonstrated that phosphomannomutase 2 (PMM2) could be a potential therapeutic target for LGG. Downregulation of PMM2 not only improved the sensitivity of LGG cells to TMZ but also directly inhibited the proliferation and migration of LGG cells. DISCUSSION: This study highlighted the association between peroxisomal FAO-related genes and poor prognosis in patients with LGG, and identified PMM2 as a candidate therapeutic target. Further studies investigating the role of peroxisomal FAO in glioma are urgently needed.