Yin Ankang, Xu Yufan, Su Xiyang, Wang Runan, Zhang Zebin, Chen Yi, Han Lu, Fu Guoxiang, Wang Wei, Wang Juan
School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Department of Pathology, Sir Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Front Oncol. 2025 Apr 1;15:1499217. doi: 10.3389/fonc.2025.1499217. eCollection 2025.
Elongation Factor Tu GTP Binding Domain Containing 2 (EFTUD2), a conserved spliceosomal GTPase, is involved in craniofacial development and various cancers, but its role in lung adenocarcinoma (LUAD) remains unclear.
EFTUD2 expression in LUAD tissues was analyzed using data from TCGA and GEO, and validated by immunohistochemistry, RT-qPCR, and Western blotting. The relationship between EFTUD2 expression and clinical features was examined using Fisher's exact test. Diagnostic and prognostic analyses were performed in R. Hub genes related to EFTUD2 were identified through topological algorithms, and immune infiltration was assessed using CIBERSORT. The cGAS-STING pathway and m6A modification were also analyzed in the TCGA LUAD cohort. Functional assays were conducted to assess EFTUD2's impact on LUAD cell proliferation, cell cycle, invasion, and metastasis, while glycolytic enzyme levels were measured by Western blotting.
EFTUD2 was upregulated in LUAD tissues and cells, correlating with N classification, visceral pleural invasion, intravascular tumor embolism, and cytokeratin-19 fragment antigen 21-1. Sixteen EFTUD2-related hub genes were identified. Higher EFTUD2 expression was linked to altered immune cell infiltration, with increased TumorPurity scores and decreased StromalScore, ImmuneScore, and ESTIMATEScore values. Gene enrichment analyses highlighted EFTUD2's involvement in cell adhesion, immune response. EFTUD2 was strongly associated with the cGAS-STING pathway and m6A modification. EFTUD2 knockdown inhibited LUAD cell proliferation, migration, and tumorigenicity, causing G0/G1 phase cell cycle arrest, and altered glycolytic enzyme expression. These findings may suggest that EFTUD2 positively regulates the progression of LUAD and modulates the glycolytic activity of tumor cells, making it valuable for LUAD treatment and prognosis.
EFTUD2 is a potential diagnostic and prognostic marker for LUAD, associated with immune infiltration, the tumor microenvironment, the cGAS-STING pathway, m6A modification, and glycolysis.
含延伸因子Tu GTP结合结构域2（EFTUD2）是一种保守的剪接体GTP酶，参与颅面发育和多种癌症，但它在肺腺癌（LUAD）中的作用仍不清楚。
利用来自癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）的数据分析EFTUD2在LUAD组织中的表达，并通过免疫组织化学、逆转录定量聚合酶链反应（RT-qPCR）和蛋白质免疫印迹法进行验证。使用Fisher精确检验来研究EFTUD2表达与临床特征之间的关系。在R语言中进行诊断和预后分析。通过拓扑算法鉴定与EFTUD2相关的枢纽基因，并使用CIBERSORT评估免疫浸润情况。还在TCGA的LUAD队列中分析了环鸟苷酸-腺苷酸合成酶-干扰素基因刺激蛋白（cGAS-STING）途径和N6-甲基腺苷（m6A）修饰。进行功能试验以评估EFTUD2对LUAD细胞增殖、细胞周期、侵袭和转移的影响，同时通过蛋白质免疫印迹法检测糖酵解酶水平。
EFTUD2在LUAD组织和细胞中上调，与N分期、脏层胸膜侵犯、血管内肿瘤栓塞和细胞角蛋白19片段抗原21-1相关。鉴定出16个与EFTUD2相关的枢纽基因。较高的EFTUD2表达与免疫细胞浸润改变有关，肿瘤纯度评分增加，基质评分、免疫评分和估计评分值降低。基因富集分析突出了EFTUD2参与细胞黏附、免疫反应。EFTUD2与cGAS-STING途径和m6A修饰密切相关。敲低EFTUD2可抑制LUAD细胞增殖、迁移和致瘤性，导致细胞周期停滞于G0/G1期，并改变糖酵解酶表达。这些发现可能表明EFTUD2正向调节LUAD的进展并调节肿瘤细胞的糖酵解活性，这使其对LUAD的治疗和预后具有重要价值。
EFTUD2是LUAD潜在的诊断和预后标志物，与免疫浸润、肿瘤微环境、cGAS-STING途径、m6A修饰和糖酵解相关。
