AUTHOR=Yin Ankang , Xu Yufan , Su Xiyang , Wang Runan , Zhang Zebin , Chen Yi , Han Lu , Fu Guoxiang , Wang Wei , Wang Juan 

TITLE=EFTUD2 is a promising diagnostic and prognostic indicator involved in the tumor immune microenvironment and glycolysis of lung adenocarcinoma

JOURNAL=Frontiers in Oncology

VOLUME=Volume 15 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1499217

DOI=10.3389/fonc.2025.1499217

ISSN=2234-943X

ABSTRACT=BackgroundElongation 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.MethodsEFTUD2 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.ResultsEFTUD2 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.ConclusionsEFTUD2 is a potential diagnostic and prognostic marker for LUAD, associated with immune infiltration, the tumor microenvironment, the cGAS-STING pathway, m6A modification, and glycolysis.