Comprehensive Multi-Omics Analysis Identifies FUT1 as a Prognostic and Therapeutic Biomarker Across Pan-Cancer

Fucosyltransferase 1 encodes a Golgi membrane protein involved in H-antigen precursor production and plays a critical role in tumor-associated glycosylation and angiogenesis. While FUT1 is known to enhance tumor stemness, adhesion, migration, and drug resistance in specific cancers, its role across diverse cancer types and its association with clinical prognosis and molecular features remain unclear. In this study, FUT1 expression was systematically analyzed across 33 cancer types using data from multiple public databases, including CCLE, TCGA, and GTEx. FUT1 expression was found to vary across cancers, correlating with poor prognosis in ACC, BLCA, and COAD and demonstrating high diagnostic accuracy in READ and COAD. Genomic analyses revealed frequent FUT1 amplifications and associations with genomic instability, while functional analyses linked FUT1 to proliferation, metastasis, and EMT pathways. FUT1 expression was also associated with immune microenvironment features, such as immune cell infiltration and stromal scores, and correlated with TMB and MSI. Drug sensitivity analysis indicated that FUT1 expression was linked to lower sensitivity to most drugs but increased sensitivity to tyrosine kinase inhibitors. Experimental validation confirmed that FUT1 knockdown inhibited proliferation, invasion, and migration in bladder, breast, and colorectal cancer cell lines, suggesting a potential role in cancer progression, though further evidence is required to fully establish its oncogenic involvement. These findings highlight FUT1 as a potential prognostic biomarker and provide insights into its biological functions and relevance for developing targeted therapeutic strategies across cancers.