Expression Of TRIM28 In Human Renal Cell Carcinoma Tissues And Its Correlation Prognosis

Objectives:TRIM28 is a member of the TRIMs family.Studies have shown that TRIM28 is involved in the occurrence and development of a variety of malignant tumors.In this paper,we intend to study the expression levels of TRIM28 in renal cell carcinoma tissues and normal tissues adjacent to cancer,and analyzed its correlation with various pathological parameters and prognostic analysis,to provide a new therapeutic target and a predictor of the prognosis for renal cell carcinoma.Methods:In this study,we collected 68 patients who underwent radical nephrectomy in the Urology Center of Qingdao Municipal Hospital affiliated to Qingdao University from June2013 to June 2016.All patients were confirmed to be renal cell carcinoma by postoperative pathological reports.Using immunohistochemistry to detect the expression of TRIM28 protein in paraffin specimens of 68 cancer tissues and corresponding 20 paracancerous tissues.Then analyze the difference between its expression in renal cell carcinoma tissues and adjacent tissues,as well as the relationship between the gender,age,tumor size,TNM stage,Fuhrman grade,and the presence or absence of lymphatic metastasis in patients with renal cell carcinoma.Using SPSS 26.0 statistical software to analyze the data.And using the Kaplan-Meier method to play the univariate survival analysis,and log-rank test was performed.Using the Cox multivariate regression model to screen the factors affecting the prognosis of patients with renal cell carcinoma.Results with P values <0.05 were considered statistically significant.Finally,the functional protein interaction network of TRIM28 was constructed using STRING and its related functional mechanism was discussed by Metascape databases.Results: The results of immunohistochemical examination of renal cancer tissue and normal tissues adjacent to cancer found that the high expression positive rates of TRIM28 protein were 67.7%(46/68)and 10.0%(2/20),respectively.Compared with paracancerous tissues,TRIM28 expression was significantly higher in renal cancer tissues,and the difference was statistically significant(P<0.01).Analysis of clinicopathological parameters revealed that the expression of TRIM28 was not associated with gender,age,tumor size,and lymph node metastasis in renal cell carcinoma patients,the difference was not statistically significant(P >0.05).However,the expression of TRIM28 was associated with TNM and Fuhrman grade of tumors.The expression of TRIM28 in stage Ⅲ-Ⅳ of TNM was higher than that in stage Ⅰ-Ⅱ,with the difference statistically significant(P < 0.05).And the expression of TRIM28 in gradeⅢ-Ⅳ of Fuhrman was higher than that in grade I-II,with the difference statistically significant(P < 0.05).The results of the prognostic analysis showed that 8 of the 68 patients were lost to follow-up,and the 5-year overall survival rate throughout the follow-up was 63.9%.Survival analysis showed that the TRIM28 expression intensity,Tumor size,TNM staging,Fuhrman grade,and lymph node metastasis were related to the prognosis of renal cancer,the difference was statistically significant(P<0.05).Further,Cox regression analysis revealed the expression level of TRIM28(P=0.012,HR=7.762),TNM staging(P=0.028,HR=2.705),Fuhrman grade(P=0.018,HR=4.832),lymph node metastasis(P<0.001,HR=8.338),and these factors are independent risk factors for the prognosis of renal cancer.Analyze the genes closely related to TRIM28 through the STRING database,and obtain a PPI network with 11 nodes and 30interactions(P<0.01).Interaction with TRIM28 are(score> 0.900)MAGEA3,MAGEC2,MDM2,UBE2 I,DAXX,HDAC1,CBX1,CBX5,SETDB1,SMARCAD1.Then through the analysis of the "Correlation" module of the GEPIA database,TRIM28 is negatively correlated with the interacting gene MDM2 in the above-mentioned PPI network,and positively correlated with the rest of the interacting genes.Among them,CBX1,HDAC1 and UBE2 I have the closest relationship with TRIM28.In addition,Using the Metascape database to perform GO enrichment analysis on TRIM28 and its closely related genes,it was found that TRIM28 and its interacting genes are mainly involved in cellular process,negative regulation of biological process,regulation of biological process,signaling,metabolic process,response to stimulus and biological regulation.Conclusion1.TRIM28 is highly expressed in renal cancer tissues.And the expression level of TRIM28 is positively correlated with the TNM staging and Fuhrman grade.It is suggested that the high expression of TRIM28 is related to the progression of renal cancer.2.TNM staging,Fuhrman grade,lymph node metastasis and TRIM28 expression level are negatively correlated with the prognosis of renal cell carcinoma.Among them,high expression of TRIM28,lymph node metastasis,TNM stage(III-IV),and Fuhrman grade(IIIIV)are all independent risk factors for the prognosis of renal cancer.3.PPI and enrichment analysis found that TRIM28 and its interacting genes are mainly involved in cellular process,negative regulation of biological process,regulation of biological process,signaling,metabolic process,response to stimulus and biological regulation.It is suggested that TRIM28 may be involved in metabolic abnormalities,signal transduction and biological regulation in renal cell carcinoma.