The Expression Of EEF1A2 And Its Correlation With Prognosis In Gastric Cancer

Purpose:Gastric cancer is the fourth most commonly diagnosed cancer and the second major cause of cancer-related death in the world, which results in 989,600 novel cases and 738,000 fatalities annually, specifically in Asian countries. In many cases, gastric cancer spreads before it is detected; hence, the majority of patients suffering from gastric cancer are diagnosed at advanced stages. Although considerable improvements have been made in high-resolution imaging, surgery techniques, chemotherapy, and radiotherapy, patients with advanced gastric cancer still face poor prognosis. The occurrence and development of gastric cancer research from the molecular genetics has gradually become the focus of the medical field.Eukaryotic elongation factor 1alpha-2(eEF1A2) is a protein translation factor involved in protein synthesis that is overexpressed in various cancers, with important functions in tumor genesis and progression. In gastric cancer, the dissection of the expression behaviour of the eukaryotic elongation factors(e EF1A2) has not yet fully elucidated. In this experiment by detecting the expression of e EF1A2 in GC tissues and normal tissues, we discussed the role of e EF1A2 in the development of gastric cancer, the relationship between clinic pathological characteristics and survival analysis, provide guidance for the early diagnosis and clinical treatment of gastric carcinoma.Methods:A subset of 46 GC tissues and 46 normal controls tissues was randomly selected by quantitative real-time PCR. A total of 129 patients with pathologically confirmed gastric cancer and 24 normal controls were recruited for this study. The expression of e EF1A2 in gastric cancer and normal tissues was evaluated by immunohistochemistry in tissue microarrays, quantitative real-time PCR and Western blot analysis. Kaplan-Meier method and Cox’s proportional hazards model were used in survival analysis.Results:A subset of 46 GC tissues and 46 normal controls tissues was randomly selected by quantitative real-time PCR. e EF1A2 m RNA transcription level was significantly elevated in gastric cancer tissues specimens compared with normal controls. This difference is significant(P = 0.008). Immunohistochemical staining of a tissue microarray containing 129 GC tissues and 24 normal controls revealed markedly elevated expression of e EF1A2 protein in GC tissues compared with that of normal controls(P < 0.01).To investigate whether e EF1A2 was also overexpressed at the protein level, we performed subsequent western blot analysis and we observed that e EF1A2 protein expression levels had a markedly increase in GC tissues in 12 paired specimens was performed and confirmed that e EF1A2 protein levels were significantly overexpressed in tumor tissue as compared with its paired normal mucosa. Kaplan-Meier analysis revealed that high e EF1A2 expressers had significantly shorter Overall Survival(median OS: 36 months 95 % CI 24.62–47.38 months) than those with low e EF1A2 expression. Multivariate analysis showed that high e EF1A2 expression could be an independent risk factor for OS(P = 0.033, HR = 1.863, 95 % CI 1.053–3.295) of GC patients. We proceeded the survival analysis using Cox’s proportional hazards regression model. We found that tumor diameter(P = 0.004), differentiation(P = 0.002), gastric wall invasion(P < 0.001), lymph node metastasis(P < 0.001), TNM stage(P < 0.001) and e EF1A2(P = 0.005) were statistically significant factors for OS in univariate analysis of Cox’s regression model. Upon a multivariate analysis, independent prognostic factors for overall survival included e EF1A2 expression, differentiation and TNM stage. We found that differentiation(P = 0.007), TNM stage(P < 0.001) and e EF1A2 expression(P = 0.033) were independent prognostic factors for the assessment of patient outcomes. Moreover, multivariate analysis confirmed that overexpression of e EF1A2 was a significant and independent indicator for predicting poor prognosis of gastric cancer.Conclusions:In conclusion, our study not only presents the first line of evidence that e EF1A2 expression is upregulated at both m RNA and protein levels in GC tissues but more importantly, shows that the high expression of e EF1A2 has a significant correlation with poor prognosis of GC patients. These findings suggest a potentially critical role of e EF1A2 in the pathogenesis and progression of GC tissues. It may provide a useful new diagnostic marker of increased levels of e EF1A2 in GC.