The Prognostic Value Of Eukaryotic Cell Translation Initiation Complex 4F For Hepatocellular Carcinoma (HCC) Patients

Objective: Hepatocellular carcinoma(HCC)is one of the most common malignant tumors in human digestive system.However,due to the occult onset of HCC,difficulty in early diagnosis,poor prognosis and easy recurrence and metastasis of patients after surgery,the treatment efficiency and effect of HCC has been greatly affected.Currently,surgical resection of tumor is the most effective treatment for HCC.Radiopharmaceuticals and targeted drugs such as sorafenib can also improve the prognosis of HCC patients.Although some progress has been made in the clinical efficacy of these therapies,the prognosis of HCC patients is still unsatisfactory.In previous studies,it was found that the proliferation of HCC cells was significantly inhibited by mutating the T37/46 phosphorylation site of 4EBP1 in HCC cell lines.Therefore,we speculate that it may be associated with the clinical prognosis of HCC patients.Therefore,this study evaluated the clinical correlation between Eukaryotic cell Translation Initiation Complex 4F(EIF4F) and prognosis of HCC patients.Methods: By screening the clinical data of 743 HCC patients in the specimen bank of our research center,a total of 86 HCC patients with complete follow-up information were screened out.The preserved tissue samples were made into tissue microarray(TMA)for immunohistochemical staining;R4.0.5 software was used for nonparametric test and analysis of experimental data and follow-up data to analyze the clinical characteristics of HCC patients;Image J software was used to analyze the optical density of tissue microarray immunohistochemical staining results,the expression of regulatory factors 4EBP1,Phop(Thr37/46)-4EBP1,EIF4 E,Phop(Ser209)-EIF4 E and EIF4 G in EIF4 F complex in HCC patients,and the correlation between their protein expression.By drawing the survival curve to analyze the relationship between Phop(Thr37/46)-4EBP1 in EIF4F and the prognosis and survival time of HCC patients;The number of tumor sites,tumor size,grade and AFP level of patients with HCC were included in multivariate regression analysis to establish Cox risk ratio model.Finally,nomogram model was constructed based on Cox risk ratio model to evaluate the value of EIF4 F on the prognosis and survival of HCC patients.Results: Four sets of tissue microarrays TMA1-4 were made,including the tissue samples of 86 HCC patients with follow-up information,including 77 male patients and 9 female patients.The median follow-up time was 48 months;Immunohistochemical staining showed that the expressions of 4EBP1,Phop(Thr37/46)-4EBP1,EIF4 E,Phop(Ser209)-EIF4 E and EIF4 G in cancer tissues were higher than those in adjacent tissues;The survival curve showed that the survival time of the nonactivated group of Phop(Thr37/46)-4EBP1 was higher than that of the activated group of Phop(Thr37/46)-4EBP1.The average survival time was 62 months and 40.7 months,respectively(P =0.038);Cox risk ratio model suggested that the most influential factor for 4EBP1 phosphorylation was the number of tumors in HCC patients,(P = 0.035);Nomogram model suggests that Phop(Thr37/46)-4EBP1 significantly affects the survival of HCC patients.Conclusion: The phosphorylation of 4EBP1(Thr37/46)in tumor tissue predicts a shorter overall survival time in HCC patients.