α-L-fucosidase isoenzymes (FUCA1/FUCA2) as prognostic markers in gliomas: a comprehensive study

α-L-fucosidases (AFU) including two isozymes (FUCA1 and FUCA2) are implicated in cancer progression, but their integrated role in glioma pathogenesis remains undefined. Using data from TCGA, CGGA, GEO, and Open GWAS, we conducted analyses to determine the significance of FUCA1 and FUCA2 in gliomas, with a particular focus on low-grade gliomas (LGG) given their clinical continuum with glioblastoma (GBM). In vitro and clinical experiments verified FUCA1 and FUCA2's functions. Results showed gliomas have a genetic link to AFU, with its overexpression and hypomethylation associated with diagnosis and poor prognosis. The high-expression group of FUCA1 and FUCA2 had a higher frequency of IDH wild-type status and lacked 1p/19q codeletion. This group also demonstrated stronger macrophage infiltration and immune gene correlation, indicating a poorer prognosis. The AFURS prognostic model, trained in TCGA-LGG + GBM and validated in CGGA mixed glioma cohorts, effectively predicted patient prognosis, and exploratorily suggested potential associations with immune therapy response. Silencing FUCA1 and FUCA2 reduced glioma cell migration, invasion, proliferation, and viability, promoting apoptosis. Interfering with FUCA2 affected the NF-kB signaling pathway. In summary, our study underscores AFU alterations' potential role in glioma progression and their value in diagnosis, treatment, and prognosis.