| Background:Endometrial Cancer(EC)is one of common malignant tumors of female reproductive tract.Most of them occur in perimenopausal and postmenopausal women.In recent years,the rate of incidence and mortality in EC are increasing.Although most patients with early diagnosis of EC have a good prognosis,there are fewer treatment options for advanced and recurrent disease because of the lack of effective targeted therapy and poor prognosis.For now,the pathogenesis of EC is not completely clear,and the means of early diagnosis and treatment for EC are limited.It is very significant to continue to explore appropriate molecular markers for the early diagnosis and targeted treatment of EC.TRIM59 protein,as a new tumor molecular marker,is highly expressed in a variety of malignant tumors.At the same time,it may be used as an oncogene to regulate the occurrence and progression of tumors.However,there are few reports on the research of TRIM59 protein in EC.Objective:1.To research the expression of TRIM59 protein in normal endometrium and EC.2.Based on bioinformatics analysis,to screen genes and regulatory pathways that may be related to TRIM59 in the occurrence and progression of endometrial cancer in TCGA database.3.To explore the relationship between the expression of TRIM59 protein and the clinicopathological features of EC.Methods:The transcriptome data of 406 endometrial cancer tissues and 19 corresponding normal tissues were obtained from TCGA database.R language was used to standardize and analyze the transcriptome data of endometrial cancer.The differential genes related to TRIM59 were screened according to the correlation coefficient>0.4,P<0.001,and then speculate the function and action pathway of TRIM59 related genes by GO and KEGG enrichment analysis.String was used to construct the PPI network of TRIM59 related proteins,and the MCC algorithm in cytohubba plug-in Cytoscape was used to determine the top 10 Hub genes of TRIM59 related genes.Sixteen pairs of endometrial cancer tissues and normal endometrium tissues were collected,and the expression of TRIM59 protein was measured by Western blot.The expression of TRIM59 in 33 cases of endometrial carcinoma and 10 cases of normal endometrium was detected by immunohistochemical staining,and the relationship between the expression difference and clinicopathological parameters was analyzed.Results:1.3097 differential genes were screened in endometrial carcinoma by taking the absolute value of log2FC>2 and the corrected P value<0.01 as the standard,1892 were up-regulated and 1205 were down-regulated,TRIM59 was up-regulated.2.107 genes related to TRIM59 were screened from the differential genes;GO functional enrichment analysis showed that TRIM59 related genes were mainly enriched in biological processes such as nuclear division,organelle fission and chromosome separation.In MF,it mainly focuses on microtubule binding and other functions.In CC,it is mainly concentrated in chromosome regions,chromosome aggregation and other cell components.3.KEGG enrichment analysis showed that TRIM59 related genes were mainly enriched in cell cycle and cell aging,viral carcinogenesis and p53 signaling pathway.4.The top 10 Hub genes of TRIM59 related genes screened from the PPI network were TTK,KIF23,CENPE,NCAPG,BUB1,BUB1B,KIF11,KIF15,DLGAP5,NUF2.5.Western blot and immunohistochemistry showed that the expression of TRIM59 in endometrial carcinoma was higher than that in normal control tissue(P<0.05).6.The expression difference of TRIM59 in endometrial carcinoma was related to pathological grade(P<0.05),but not related to age,pathological type,lymph node metastasis,FIGO stage,menopause and depth of invasion(P>0.05).Conclusion:The expression level of TRIM59 protein in endometrial carcinoma was higher than that in normal endometrium,suggesting that TRIM59 protein may be related to the occurrence and progression of endometrial carcinoma.Immunohistochemical results showed that the expression level of TRIM59 protein was correlated with the degree of pathological differentiation,suggesting that the up-regulated expression of TRIM59 may affect the malignant degree of endometrial carcinoma,it is speculated that TRIM59 can be used as an indicator for early diagnosis of endometrial carcinoma. |
