High expression of eIF4A1 promotes angiogenesis through the NF‑&kappa;B/VEGFA pathway and predicts poor prognosis in gastric cancer

Zhu,Xiaoqun; Jia,Lizhou; Kuai,Xingwang; Tang,Qi; Chang,Xinxia; Zhang,Xiao; Chen,Bing; Zhi,Hui; Hu,Haoran; Huang,Xiaomei; Feng,Zhenqing; Huang,Wenbin

doi:10.3892/or.2025.8951

High expression of eIF4A1 promotes angiogenesis through the NF‑κB/VEGFA pathway and predicts poor prognosis in gastric cancer

Authors:
- Xiaoqun Zhu
- Lizhou Jia
- Xingwang Kuai
- Qi Tang
- Xinxia Chang
- Xiao Zhang
- Bing Chen
- Hui Zhi
- Haoran Hu
- Xiaomei Huang
- Zhenqing Feng
- Wenbin Huang
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Affiliations: 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, Department of Pathology, Medical School of Nantong University, Nantong, Jiangsu 226000, P.R. China, Department of Pathology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471000, P.R. China
Published online on: July 17, 2025 https://doi.org/10.3892/or.2025.8951
Article Number: 118
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 χ² 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 in vivo. 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.

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