Yin Haofeng, Xue Yibo, Wang Chen, Wu Yanqin, Guo Yuchen, Li Chunzhen, Zhang Yunyan, Yin Shulei, Zhao Tiejun
Institute of Immunology, School of Basic Medicine, Naval Medical University, Shanghai, China.
Department of Thoracic Surgery, Changhai Hospital, Naval Medical University, Shanghai, China.
Front Immunol. 2025 Aug 11;16:1636503. doi: 10.3389/fimmu.2025.1636503. eCollection 2025.
Lung adenocarcinoma (LUAD) represents a significant global health burden. The absence of reliable biomarkers and the heterogeneity in treatment responses continue to hinder improvements in patient prognosis. This study aimed to identify novel biomarkers capable of predicting patient outcomes and therapeutic responsiveness, while also assessing their potential as intervention targets for LUAD.
Multiple cohorts from public databases were employed to screen key prognostic genes, followed by external validations. Clinicopathological indicators were integrated to analyze the independent prognostic role of the key gene UBE2N and its association with LUAD progression. Functional enrichment analysis elucidated the biological mechanisms regulated by UBE2N. Differences in immune microenvironment components, immunoregulatory gene expression, and immune functional activities between subgroups stratified by UBE2N expression levels. The role of UBE2N in predicting tumor therapeutic susceptibility was characterized using bioinformatics algorithms combined with publicly available CRISPR screening datasets and immunotherapy cohorts. Immunohistochemistry, cell viability, and apoptosis experiments were conducted to verify the oncogenic effects of UBE2N.
UBE2N was identified as an independent prognostic biomarker for LUAD. Elevated UBE2N expression correlated with poorer patient survival rates and advanced disease stages. Genes associated with UBE2N were significantly enriched in critical cellular processes, including DNA replication, nucleosome assembly, and neutrophil extracellular trap formation. High-UBE2N tumors exhibited enhanced cell cycle, DNA replication, and oxidative phosphorylation activities. Low-UBE2N tumors exhibit elevated proportions of intratumoral NK cells, dendritic cells, effector T cells, and enhanced antigen processing and presentation. UBE2N was a potential promoter of immune evasion and drug resistance, with its high expression suggestive of low responsiveness to cancer immunotherapy and targeted therapies. Three potential UBE2N-inhibiting compounds were identified. Tissue microarrays confirmed UBE2N overexpression in LUAD, correlating with tumor size, while UBE2N knockdown suppressed tumor cell viability and induced apoptosis.
UBE2N may serve as a promising prognostic biomarker and therapeutic target for LUAD. Inhibition of UBE2N is expected to suppress LUAD progression and enhance therapeutic efficacy.
肺腺癌（LUAD）是一项重大的全球健康负担。缺乏可靠的生物标志物以及治疗反应的异质性持续阻碍患者预后的改善。本研究旨在识别能够预测患者预后和治疗反应性的新型生物标志物，同时评估它们作为LUAD干预靶点的潜力。
利用来自公共数据库的多个队列筛选关键预后基因，随后进行外部验证。整合临床病理指标以分析关键基因UBE2N的独立预后作用及其与LUAD进展的关联。功能富集分析阐明了UBE2N调控的生物学机制。按UBE2N表达水平分层的亚组之间免疫微环境成分、免疫调节基因表达和免疫功能活性的差异。使用生物信息学算法结合公开可用的CRISPR筛选数据集和免疫治疗队列来表征UBE2N在预测肿瘤治疗敏感性中的作用。进行免疫组织化学、细胞活力和凋亡实验以验证UBE2N的致癌作用。
UBE2N被鉴定为LUAD的独立预后生物标志物。UBE2N表达升高与较差的患者生存率和晚期疾病阶段相关。与UBE2N相关的基因在关键细胞过程中显著富集，包括DNA复制、核小体组装和中性粒细胞胞外陷阱形成。高UBE2N肿瘤表现出增强的细胞周期、DNA复制和氧化磷酸化活性。低UBE2N肿瘤表现出肿瘤内NK细胞、树突状细胞、效应T细胞比例升高，以及抗原加工和呈递增强。UBE2N是免疫逃逸和耐药性的潜在促进因子，其高表达提示对癌症免疫治疗和靶向治疗的低反应性。鉴定出三种潜在的UBE2N抑制化合物。组织微阵列证实LUAD中UBE2N过表达，与肿瘤大小相关，而UBE2N敲低抑制肿瘤细胞活力并诱导凋亡。
UBE2N可能是LUAD有前景的预后生物标志物和治疗靶点。抑制UBE2N有望抑制LUAD进展并提高治疗效果。
