Over-expression of eukaryotic translation initiation factor 4 gamma 1 correlates with tumor progression and poor prognosis in nasopharyngeal carcinoma

Abstract

BackgroundThe aim of the present study was to analyze the expression of eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) in nasopharyngeal carcinoma (NPC) and its correlation with clinicopathologic features, including patients' survival time.MethodsUsing real-time PCR, we detected the expression of EIF4G1 in normal nasopharyngeal tissues, immortalized nasopharyngeal epithelial cell lines NP69, NPC tissues and cell lines. EIF4G1 protein expression in NPC tissues was examined using immunohistochemistry. Survival analysis was performed using Kaplan-Meier method. The effect of EIF4G1 on cell invasion and tumorigenesis were investigated.ResultsThe expression levels of EIF4G1 mRNA were significantly greater in NPC tissues and cell lines than those in the normal nasopharyngeal tissues and NP69 cells (P < 0.001). Immunohistochemical analysis revealed that the expression of EIF4G1 protein was higher in NPC tissues than that in the nasopharyngeal tissues (P < 0.001). In addition, the levels of EIF4G1 protein in tumors were positively correlated with tumor T classification (P = 0.039), lymph node involvement (N classification, P = 0.008), and the clinical stages (P = 0.003) of NPC patients. Patients with higher EIF4G1 expression had shorter overall survival time (P = 0.019). Multivariate analysis showed that EIF4G1 expression was an independent prognostic indicator for the overall survival of NPC patients. Using shRNA to knock down the expression of EIF4G1 not only markedly inhibited cell cycle progression, proliferation, migration, invasion, and colony formation, but also dramatically suppressed in vivo xenograft tumor growth.ConclusionOur data suggest that EIF4G1 can serve as a biomarker for the prognosis of NPC patients.

Exome sequencing reveals mutant genes with low penetrance involved in MEN2A-associated tumorigenesis

“…We chose to examine the oncogenic potential of EIF4G1, which regulates the initiation of translation of mRNAs encoding mitochondrial, cell survival, and cell-growth-associated genes in response to different stresses (Ramírez-Valle et al 2008, Silvera et al 2009). Overexpression of EIF4G1 was observed in breast cancer and nasopharyngeal carcinoma, and treatment with rapamycin mediated downregulation of the gene in breast cancer (Silvera et al 2009, Tu et al 2010. In two human MTC cell lines and a rat pheochromacytoma cell line, we found that ectopic expression of mutant EIF4G1 increases cell proliferation in a background of WT gene expression.…”

“…Among the 13 genes with either SNVs or copy number alterations, we further investigated the functional roles of EIF4G1 and GRAP in MTC and PCC cell lines because of their previously described association with malignancy (Feng et al 1996, Silvera et al 2009, Tu et al 2010, Patel et al 2012.…”

Integrin αvβ6 sets the stage for colorectal cancer metastasis

“…In nasopharyngeal cancers, Tu et al demonstrated that eIF4G1 mRNA and protein expression was significantly elevated in the tumour compared to nine surrounding tissue, where it positively correlated with TNM-staged tumour progression and reduced survival time [53]. Tu et al also highlighted that inhibiting expression of eIF4G1 by shRNA resulted in the suppression of cell migration/invasion, proliferation/cell cycle progression, colony formation and xenograft tumour growth in vivo [53].…”

“…Collectively, this suggests that significant upregulation of eIF4G1 with β6 expression may facilitate an altered translational programme, influencing the expression of downstream proteins. eIFG1 is also an effector of mTOR signalling activity (following its phosphorylation) and has been observed to be elevated in breast [52], nasopharyngeal [53] and squamous cell lung cancers [54] where it is associated with metastatic progression and poor patient survival. Badura et al identified that elevated eIF4G1 expression in breast cancer selectively increased the translation of mRNAs involved in promoting cell survival, the prevention of apoptosis and autophagy following genotoxic DNA damage [48].…”

Proteomics and translational medicine: molecular biomarkers for cancer diagnosis, prognosis and prediction of therapy outcome

“…It has been detected that NPC patients with higher eukaryotic translation initiation factor 4 g1 (EIF4G1) expression had shorter overall survival. Using shRNA to knock down the expression of EIF4G1 not only markedly inhibited cell cycle progression, proliferation, migration, invasion and colony formation, but also dramatically suppressed in vivo xenograft tumor growth [19].…”