| 【Objective】To detect the expression of eukaryotic initiation factor 4E（eIF4E）and cyclin D1 in endometrial Carcinoma（EC）,the expression significance of eIF4E and Cyclin D1 in EC was explored,which provided new ideas for EC diagnosis.【Methods】1.Bioinformatics analysis:using the data information in the GEPIA database,the expression differences of eIF4E and Cyclin D1 in EC and normal endometrial tissues were analyzed;The Kaplan-Meier Plotter database was used to analyze the effects of eIF4E and Cyclin D1 expression on the prognosis of EC patients such as Overall Survival（OS）and Disease Free Survival（DFS）.The Linked Omics database was used to find and analyze the relevant genes of eIF4E and Cyclin D1 coexpression.The STRING database was used to construct a protein interaction model of eIF4E and Cyclin D1.The relationship between eIF4E and Cyclin D1 and EC immune cell infiltration was explored using the TIMER database.The UALCAN database was used to explore the methylation of eIF4E and Cyclin D1 in EC.2.Experiment:（1）Select the surgically removed endometrial lesion tissue wax block archived from October 1,2020 to January 1,2022,and all have a clear pathological diagnosis.Among them,there were 28 cases of EC tissue,21 cases of endometrial dysplastic tissue,and 23 cases of normal endometrial tissue.The protein expression levels of eIF4E and Cyclin D1 in tissue paraffin sections were detected by immunohistochemistry（SP method）.（2）Collect the clinicopathological information of EC patients and analyze the relationship between eIF4E and Cyclin D1 and clinicopathological features.（3）The correlation between eIF4E and Cyclin D1 expression in EC was analyzed by Kappa test.（4）The diagnostic efficacy of eIF4E and Cyclin D1 on EC was evaluated by ROC curve.（5）SPSS22.0 software was used to statistically collect all experimental results.【Results】1.Bioinformatics analysis:（1）GEPIA database:eIF4E and Cyclin D1 are abnormally expressed in a variety of tumors,The expression of Cyclin D1 in EC was higher than that of normal endometrium（P<0.05）,there was no significant difference in the expression of eIF4E in normal endometrium and EC（P>0.05）,there was no significant difference in the expression of eIF4E and Cyclin D1 in EC stage（P>0.05）,and the expression of eIF4E and Cyclin D1in EC was correlated（P<0.01,R=0.2）.（2）Kaplan-Meier Plotter database:the expression of eIF4E is related to the prognosis of the patient’s DFS（P<0.01）,not related to the patient’s OS（P>0.05）,and the expression of Cyclin D1 is not related to the patient’s prognosis such as OS and DFS（P>0.05）.（3）Linked Omics database:eIF4E and its co-expression genes participate in biological regulation,cell proliferation and growth,cell metabolism and other biological processes through the exercise of proteins,nucleic acid binding and various enzymatic reactions,and are closely related to ubiquitination signaling pathway,P53 signaling pathway and TGF-βsignaling pathway,etc.Cyclin D1 and its co-expression genes participate in biological processes such as regulating cell cycle,controlling cell proliferation,differentiation,etc.,and are closely related to Wnt signaling pathway,TGF-βsignaling pathway and TNF signaling pathway are closely related.（4）STRING database:The 10 proteins with the closest effect of eIF4E mainly participate in biological functions such as ubiquitination,phosphorylation,immune cell activation,and neutrophil transport,and the 10 proteins with the closest effect of Cyclin D1 mainly participate in cellular immunity,accelerate cell proliferation,regulate cell cycle and other biological functions.（5）TIMER database:the expression level of eIF4E was positively correlated with CD8+T cells（r=0.41,P=3.91e-13）,macrophages（r=0.054,P=3.61e-01）,neutrophils（r=0.17,P=3.58e-03）and dendritic cells（r=0.185,P=1.51e-03）,which was statistically significant;The expression levels of Cyclin D1 were positively correlated with CD8+T cells（r=0.252,P=1.29e-05）,neutrophils（r=0.177,P=2.31e-03）and dendritic cells（r=0.223,P=1.22e-04）,which was statistically significant.（6）UALCAN database:methylation of eIF4E and Cyclin D1 is correlated with EC（P<0.01）.2.Immunohistochemical test:（1）The positive rates of eIF4E in EC,dysplasia and normal endometrial tissues were 82.14%（23/28）,61.90%（13/21）and 13.04%（3/23）,respectively,and the difference was statistically significant（P<0.01）;the expression of eIF4E in EC was not correlated with age,depth of muscular invasion,pathological stage,degree of tissue differentiation and lymph node metastasis（P>0.05）.（2）The positive rates of Cyclin D1 in EC,dysplasia and normal endometrial tissues were 96.4%（27/28）,42.90%（9/21）and 8.7%（2/23）,respectively,and the difference was statistically significant（P<0.01）.The expression of Cyclin D1 in EC was not correlated with age,depth of muscular invasion,pathological stage,degree of tissue differentiation,and lymph node metastasis（P>0.05）.（3）Kappa test analyzed that eIF4E and Cyclin D1 were correlated in EC（k=0.291,P<0.05）.（4）The diagnostic efficacy of eIF4E and Cyclin D1 against EC was evaluated by ROC curve,and the results showed that AUC eIF4E+Cyclin D1（0.929）>AUC Cyclin D1（0.909）>AUC eIF4E（0.902）.The combined detection of eIF4E and Cyclin D1 improves the diagnostic performance of EC.【Conclusion】1.eIF4E and Cyclin D1 were highly expressed in EC tissues,and there was positively correlation between them;2.The expression of eIF4E and Cyclin D1 was independent of the age,depth of muscular invasion,lymphatic metastasis,degree of tissue differentiation and pathological stage of EC patients.eIF4E expression was dependent of DFS but not OS in patients;Cyclin D1 expression was independent of DFS and OS.3.eIF4E and Cyclin D1 have early diagnostic value for EC,and the joint diagnosis is more effective. |
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