EIF3B is associated with poor outcomes in gastric cancer patients and promotes cancer progression via the PI3K/AKT/mTOR signaling pathway

Lin Wang,1,2 Xianzi Wen,1 Fengming Luan,1 Tao Fu,2 Chao Gao,2 Hong Du,1 Ting Guo,1 Jing Han,1 Longtao Huangfu,1 Xiaojing Cheng,1 Jiafu Ji1,21Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China; 2Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of ChinaCorrespondence: Xiaojing ChengKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing 100142, People’s Republic of ChinaTel +86 108 819 6760Email chengli@bjmu.edu.cnJiafu JiKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, People’s Republic of ChinaTel +86 108 819 6048Email jijiafu@hsc.pku.edu.cnPurpose: Eukaryotic translation initiation factor (EIF) plays a vital role in protein synthesis. EIF3B is a core subunit of the EIF3 family, and is overexpressed in many tumors. EIF3B is associated with an unfavorable prognosis, as well as the genesis and development of tumors. However, the potential role of EIF3B in gastric cancer (GC) remains unknown. In the current study, we explored the clinical significance and the possible mechanism of EIF3B in the progression of GC.Methods: EIF3B expression was analyzed in 78 GC tissue samples through quantitative PCR and in 94 GC tissue samples through immunohistochemistry (IHC) staining. The correlation between EIF3B and clinicopathological features was analyzed in GC tissues. The role of EIF3B in GC progression was investigated through in vitro and in vivo assays.Results: EIF3B expression was upregulated in GC tissues (73.4%, IHC). High expression of EIF3B was significantly correlated with the depth of tumor invasion, lymph node metastasis and TNM stage (P=0.000, 0.000 and 0.000, respectively). Multivariate analysis indicated that GC patients with high EIF3B expression suffered a poorer 5-year survival. EIF3B promoted GC cell proliferation and was strongly associated with proliferating cell nuclear antigen (PCNA) expression in GC samples (P=0.009). It also enhanced tumor cell migration and invasion, which were affected through epithelial-mesenchymal transition (EMT) and the Stat3 signaling pathway. Knockdown of EIF3B in GC cells suppressed the growth of xenograft tumors and lung metastatic colonization in vivo. Furthermore, gene set enrichment analysis (GSEA) and Western blot results demonstrated that EIF3B activated the PI3K/AKT/mTOR signaling pathway.Conclusion: Our results suggest that EIF3B plays an oncogenic role in GC progression and serves as an independent prognostic factor for GC patients.Keywords: EIF3B, gastric cancer, prognosis, PI3K/AKT/mTOR pathway