Yu Zhe, Luo Jing, An Wen, Wei Herui, Li Mengqi, He Lingling, Xiao Fan, Wei Hongshan
Department of Gastroenterology, Peking University Ditan Teaching Hospital, Beijing 100015, China.
Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.
Biomedicines. 2025 Mar 22;13(4):773. doi: 10.3390/biomedicines13040773.
: The EGF domain-specific O-GlcNAc transferase (EOGT), a migrasome marker, plays emerging roles in cancer biology through O-GlcNAcylation modifications, yet its pan-cancer functions and therapeutic implications remain underexplored. This study aimed to systematically characterize EOGT's oncogenic mechanisms across malignancies, with particular focus on hepatocellular carcinoma (HCC) progression and sorafenib resistance. : Multi-omics analysis integrated TCGA/GTEx data from 33 cancer types with spatial/single-cell transcriptomics and 10 HCC cohorts. Functional validation employed Huh7 cell models with modulation, RNA sequencing, and ceRNA network construction. Drug sensitivity analysis leveraged GDSC/CTRP/PRISM databases, while immune microenvironment assessment utilized ESTIMATE/TIMER algorithms. : showed cancer-specific dysregulation, marked by significant upregulation in HCC correlating with advanced stages and poor survival. Pan-cancer analysis revealed 's association with genomic instability, tumor stemness, and angiogenesis. Experimental validation demonstrated EOGT's promotion of HCC proliferation and migration. A novel exosomal circ_0058189/miR-130a-3p/EOGT axis was identified, showing that circ_0058189 was upregulated in HCC tissues, plasma samples and exosomes of sorafenib-resistant cells. : This study establishes EOGT as a pan-cancer angiogenesis biomarker, while elucidating its role in therapeutic resistance via exosomal circRNA-mediated regulation, providing mechanistic insights for targeted intervention strategies.
表皮生长因子(EGF)结构域特异性O-连接N-乙酰葡糖胺转移酶(EOGT)是一种迁移体标志物,通过O-连接N-乙酰葡糖胺化修饰在癌症生物学中发挥着新出现的作用,但其在泛癌中的功能及治疗意义仍未得到充分探索。本研究旨在系统地阐明EOGT在各种恶性肿瘤中的致癌机制,尤其关注肝细胞癌(HCC)的进展及对索拉非尼的耐药性。:多组学分析整合了来自33种癌症类型的TCGA/GTEx数据以及空间/单细胞转录组学数据和10个HCC队列的数据。功能验证采用对Huh7细胞模型进行调控、RNA测序及构建ceRNA网络的方法。药物敏感性分析利用了GDSC/CTRP/PRISM数据库,而免疫微环境评估则采用了ESTIMATE/TIMER算法。:结果显示癌症特异性失调,其特征为在HCC中显著上调,且与晚期阶段及不良生存相关。泛癌分析揭示了其与基因组不稳定性、肿瘤干性及血管生成的关联。实验验证表明EOGT可促进HCC的增殖和迁移。还鉴定出了一种新的外泌体circ_0058189/miR-130a-3p/EOGT轴,结果显示circ_0058189在HCC组织、血浆样本及索拉非尼耐药细胞的外泌体中表达上调。:本研究确立了EOGT作为一种泛癌血管生成生物标志物的地位,同时阐明了其通过外泌体circRNA介导的调控在治疗耐药中的作用,为靶向干预策略提供了机制性见解。