Zhu Xiaoqun, Jia Lizhou, Kuai Xingwang, Tang Qi, Chang Xinxia, Zhang Xiao, Chen Bing, Zhi Hui, Hu Haoran, Huang Xiaomei, Feng Zhenqing, Huang Wenbin
Department of Pathology, Wannan Medical College, Wuhu, Anhui 241002, P.R. China.
National Health Commission Key Laboratory of Antibody Techniques, Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China.
Oncol Rep. 2025 Oct;54(4). doi: 10.3892/or.2025.8951. Epub 2025 Jul 19.
Increased eukaryotic translation initiation factor 4A (eIF4A1) expression is observed in numerous types of cancer and is associated with carcinogenesis; however, little is known about the role of eIF4A1 in gastric cancer (GC) angiogenesis. In the present study, a total of 1,758 gastric mucosa samples were collected for immunohistochemical staining in tissue microarrays. The expression levels of eIF4A1 and their association with clinicopathological characteristics and prognosis were analyzed using χ test and univariate/multivariate analysis. The effects of abnormal eIF4A1 expression in GC cells on proangiogenic activity was detected using the Cell Counting Kit‑8 proliferation assay, wound healing assay, Transwell assay, angiogenesis assay and a subcutaneous tumor model. The role of eIF4A1 in tumor‑infiltrating lymphocytes was explored using bioinformatics analysis. Furthermore, the effect of eIF4A1 on proangiogenic factors was confirmed by the quantitative polymerase chain reaction and western blotting. Notably, eIF4A1 was highly expressed in GC tissues, and was associated with patient age, tumor differentiation, depth of invasion, distant metastasis and Tumor‑Node‑Metastasis stage. Furthermore, it was suggested that high eIF4A1 expression could be regarded as a poor prognostic biomarker for patients with GC. The expression levels of eIF4A1 in GC cells were also positively related to proliferation, migration and the tube formation of human umbilical vein endothelial cells, and microvessel density . Furthermore, eIF4A1 in GC cells regulated the infiltration of immune cells in the tumor microenvironment, and promoted the expression of VEGFA and NF‑κB. In conclusion, eIF4A1 may promote GC angiogenesis through the NF‑κB/VEGFA pathway, and could be considered an independent prognostic biomarker for patients with GC.
在多种癌症中均观察到真核生物翻译起始因子4A(eIF4A1)表达增加,且其与致癌作用相关;然而,关于eIF4A1在胃癌(GC)血管生成中的作用却知之甚少。在本研究中,共收集了1758份胃黏膜样本用于组织芯片的免疫组织化学染色。使用χ检验和单因素/多因素分析来分析eIF4A1的表达水平及其与临床病理特征和预后的关系。使用细胞计数试剂盒-8增殖试验、伤口愈合试验、Transwell试验、血管生成试验和皮下肿瘤模型检测GC细胞中异常eIF4A1表达对促血管生成活性的影响。通过生物信息学分析探索eIF4A1在肿瘤浸润淋巴细胞中的作用。此外,通过定量聚合酶链反应和蛋白质印迹法证实了eIF4A1对促血管生成因子的影响。值得注意的是,eIF4A1在GC组织中高表达,且与患者年龄、肿瘤分化、浸润深度、远处转移和肿瘤-淋巴结-转移分期相关。此外,提示eIF4A1高表达可被视为GC患者预后不良的生物标志物。GC细胞中eIF4A1的表达水平还与人脐静脉内皮细胞的增殖、迁移和管腔形成以及微血管密度呈正相关。此外,GC细胞中的eIF4A1调节肿瘤微环境中免疫细胞的浸润,并促进VEGFA和NF-κB的表达。总之,eIF4A1可能通过NF-κB/VEGFA途径促进GC血管生成,并且可被视为GC患者的独立预后生物标志物。