Liu Yunqing, Chen Guanjun, Yuan Xiaotian, Chen Yaxin, Cui YuJie, Cao Ke
Department of Oncology, Third Xiangya Hospital of Central South University, Changsha, 410013, China.
Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, 410008, China.
Int J Med Sci. 2025 Feb 18;22(6):1313-1328. doi: 10.7150/ijms.108072. eCollection 2025.
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.
岩藻糖基转移酶1编码一种参与H抗原前体产生的高尔基体膜蛋白，在肿瘤相关糖基化和血管生成中起关键作用。虽然已知FUT1在特定癌症中可增强肿瘤干性、黏附、迁移和耐药性，但其在不同癌症类型中的作用及其与临床预后和分子特征的关联仍不清楚。在本研究中，利用来自多个公共数据库（包括CCLE、TCGA和GTEx）的数据，对33种癌症类型的FUT1表达进行了系统分析。发现FUT1表达在不同癌症中存在差异，与ACC、BLCA和COAD的不良预后相关，在READ和COAD中具有较高的诊断准确性。基因组分析揭示了FUT1的频繁扩增及其与基因组不稳定的关联，而功能分析将FUT1与增殖、转移和EMT途径联系起来。FUT1表达还与免疫微环境特征相关，如免疫细胞浸润和基质评分，并与TMB和MSI相关。药物敏感性分析表明，FUT1表达与对大多数药物的较低敏感性相关，但与对酪氨酸激酶抑制剂的敏感性增加相关。实验验证证实，FUT1敲低可抑制膀胱、乳腺和结肠癌细胞系的增殖、侵袭和迁移，提示其在癌症进展中可能发挥作用，不过需要进一步证据来充分证实其致癌作用。这些发现突出了FUT1作为一种潜在的预后生物标志物，并为其生物学功能以及在开发跨癌症靶向治疗策略中的相关性提供了见解。
