Study The Clinical Significance Of The P-eIF4E, P-Nnk1and P-4EBP1Proteins Expression In The Nasopharyngeal Carcinoma

Objective:In order to investigate the correlation between expression of p-eIF4E, p-Mnkl and p-4EBPl proteins and the clinicopathological features and prognosis in the nasopharyngeal carcinoma (nasopharyngeal carcinoma, NPC), and screen the molecular markers for clinical progression and prognosis of NPC.Methods:①We collected314cases of paraffin-embedded NPC specimens from biopsy or surgical resection in the second Xiangyia hospital, which included primary cancer, recurrence and metastatic cancer. All of the cases had the complete clinical and pathological information, and272patients had the long-term and complete follow-up information.②Immunohistochemical MaxVisionTM/HRP method was used to detect the expression of p-eIF4El, p-Mnk and p-4EBPl proteins in NPC tissues.③The relationships between expression of p-eIF4E, p-Mnk1and p-4EBPl proteins and clinicopathological features of NPC such as recurrence, metastasis and survival status were analyzed by chi-squared test (x2). Spearman’s correlation analysis was hired to analyze the correlation of the proteins expression of p-4EBPl, p-eIF4E and p-Mnkl proteins in NPC. We used the Kaplan-Meier survival analysis to analyze the relationships between expression of p-eIF4E, p-Mnkl and p-4EBPl proteins and the survival time of NPC. Multivariable Cox regression analysis was applied to assess whether p-eIF4E, p-Mnkl and p-4EBPl proteins can used as the molecular markers for independently predicted survival status of NPC. Effectiveness of the predictive value of p-eIF4E, p-Mnkl and p-4EBP1proteins expression in NPC were estimated by comparing the sensitivity, specificity, positive predictive value, negative predictive value and accuracy rate. Calculations were performed by SPSS16.0statistical software for windows, with level of two-sided test P<0.05to determine significant differences.Results:①The abnormal over-expression of p-eIF4E, p-Mnkl and p-4EBPl proteins was found in the NPC, and positive percentage of p-eIF4E, p-Mnkl and p-4EBPl proteins was74.2%(233/314),81.5%(256/314),72.9%(229/314), respectively. The p-eIF4E and p-Mnkl proteins expression in NPC with lymph node metastasis were evidently higher than that in NPC without lymph node metastasis (P<0.05,P<0.05); and the positive percentage of p-eIF4E, p-Mnkl and p-4EBPl proteins expression in group of dead NPC patients were significantly higher than that in the group of live NPC patients (P<0.05, P＜0.001, P＜0.05, respectively); but there were no significant correlation between proteins expression of p-eIF4E, p-Mnk1and p-4EBP1and pathological type, clinical stage, age and gender in NPC (P>0.05).②The positive percentage of p-eIF4E protein expression in the metastatic cancer of NPC were significantly higher than that in the primary cancer of NPC (P<0.05), but the positive percentage of p-4EBP1protein expression in the metastatic cancer of NPC were significantly lower than that in the primary cancer of NPC in NPC primary cancer (P<0.01). There were no significant correlation between positive expression of the p-Mnk1protein and the primary cancer and metastasis cancer of NPC (.P>0.05), also, there were no significant correlation between the positive percentage of the p-eIF4E, p-Mnk1and p-4EBP1proteins expression and in the primary cancer and the recurrence cancer ofNPC(P>0.05).③The Spearman’s relevant analysis indicated that the expression of the p-eIF4E protein had significantly positive correlation with that of the p-Mnk1and p-4EBP1proteins in NPC tissues (r=0.343, P＜0.001; r=0.185, P＝0.002, respectively), and there was significantly positive correlation between expression of p-Mnk1protein and that of p-4EBP1in NPC (r=0.133,P＝0.028).④The Kaplan-Meier survival analysis showed that the survival time of NPC patients with positive expression of p-eIF4E, p-Mnk1and p-4EBP1proteins were significantly lower than that of these patients with no expression of p-eIF4E, p-Mnk1and p-4EBP1proteins (P=0.003; P＜0.001, P=0.02, respectively).⑤The multivariable Cox regression analysis showed that the positive expression of p-eIF4E and p-Mnk1proteins was the independent prognostic molecular markers of NPC.⑥The sensitivity, specificity, positive predictive value, negative predictive value and accuracy rate analysis showed that the combined detection of p-eIF4E, p-Mnk1and p-4EBP1proteins expression may be one better molecular markers to evaluate the NPC clinical prognosis.Conclusions:①The abnormal over-expression of p-eIF4E, p-Mnk1and p-4EBP1proteins had a significant positive correlation with each other in NPC.②The expression of p-eIF4E, p-Mnk1proteins might promote lymph node metastasis in NPC.③The survival time of NPC patients with the expression of p-eIF4E, p-Mnk1and p-4EBP1proteins was significantly shorter than the patients without expression of p-eIF4E, p-Mnk1and p-4EBP1proteins. The NPC patients with positive expression of p-eIF4E or p-Mnk1proteins had poor prognosis, and p-eIF4E or p-Mnk1protein was the independent prognostic molecular marker of NPC.④The combined detection of p-eIF4E, p-Mnk1and p-4EBP1proteins expression was the better molecular markers to predict prognosis of the NPC.