Multi-omic Characterization of Protein O-Fucosyltransferases POFUT1 and POFUT2 as Novel Prognostic Biomarkers and Immune Modulators in Epithelial Ovarian Cancer

Background: Epithelial ovarian cancer (EOC) remains the most fatal gynecological malignancy worldwide, with 5-year survival rates of only 30%–45%. Aberrant glycosylation, especially fucosylation mediated by protein O-fucosyltransferases 1 and 2 (POFUT 1 and POFUT 2), plays a key role in tumor progression. However, their expression patterns, immunoregulatory functions, and prognostic significance in ovarian cancer (OC) remain unclear. Methods: A comprehensive bioinformatics analysis was conducted by using five independent Gene Expression Omnibus datasets (GSE59091, GSE52037) and The Cancer Genome Atlas OC data. Differential expression analysis, pathway enrichment, protein–protein interaction network, and survival analyses were carried out. Tumor immune microenvironment associations were evaluated using CIBERSORT, TIMER2.0, and ESTIMATE. Results: Hierarchical clustering analysis showed that the expression of 11 out of 13 fucosyltransferase family members increased in a coordinated manner, with POFUT1 and POFUT2 serving as regulatory hubs. High POFUT expression significantly improved overall survival (hazard ratios [HR] = 0.76, P = 0.00067) and progression-free survival (HR = 0.84, P = 0.014). POFUT2 demonstrated constantly protective effects across multiple probe sets. Remarkably, POFUT1 and POFUT2 diametrically opposed immune correlation profiles, POFUT1 positively correlated with immunosuppressive M2 macrophages and negatively with CD8+ T cells, while POFUT2 showed opposite patterns. Multi-omics analysis revealed distinct regulatory mechanisms for each protein. Conclusion: POFUT1 and POFUT2 are both promising biomarkers for predicting cancer clinical prognosis and have specific immunoregulatory functions in OC, thus necessitating biomarker-based therapeutic strategies rather than large-scale inhibition of signaling pathways.