Expression And Clinical Significance Of TNFAIP3 In Clear Cell Renal Cell Carcinoma

BackgroundRenal cell carcinoma(RCC)accounts for about 85% of kidney malignancies,with clear cell renal cell carcinoma(ccRCC)being the most common.Patients with ccRCC have few early symptoms,while those with clinical symptoms are diagnosed at a later stage.Currently,surgical resection is the standard treatment for early stage renal cell carcinoma,but surgical treatment is not effective for advanced stage renal cell carcinoma,especially for patients with recurrence/metastasis,and the 3-year survival rate is less than20%.Therefore,exploring the mechanisms of ccRCC can lead to new therapeutic targets,which are important for improving the prognosis of patients and assessing their prognosis.In recent years,Tumor necrosis factor alpha induced protein3(TNFAIP3)has been found to inhibit the progression of lymphoma,colorectal cancer,hepatocellular liver cancer,pancreatic cancer,lung cancer and also promote the development of breast,gastric and bladder cancers.It can also promote the development of breast cancer,stomach cancer,malignant melanoma and bladder cancer.Biological functions of TNFAIP3 mainly focus on the regulation of NF-κB signaling pathway and apoptosis.In addition,TNFAIP3 is also involved in metabolism and autophagy.NF-κB signaling pathway is mainly involved in cell response to external stimuli,such as cytokines,and plays an important role in the inflammatory response,immune response,etc.Its dysregulation may cause autoimmune diseases,chronic inflammation and malignancies.TNFAIP3 is an intracellular inhibitor of NF-κB signaling pathway and plays a key role in the regulation of this pathway.The biochemical structure of TNFAIP3 determines that it has two functions of ubiquitin ligase and deubiquitin enzyme activity.Whether TNFAIP3 removes K63 or K48 polyubiquitinated chains and the underlying mechanism of its ubiquitin ligases are still of interest to many investigators.TNFAIP3 as protein factors,is closely related to the development of tumor research TNFAIP3 different roles and functions in various tumors in the mechanism can provide diagnostic tool for clinical doctors and provide new treatments for patients.ObjectiveFor TNFAIP3 in urinary bladder tumors,some researchers have explored the abnormal expression of TNFAIP3 in bladder inflammatory tissues and tumor tissues,revealing that TNFAIP3 is positively correlated with the occurrence and development of bladder tumors.Subsequently,in examining its relationship with the clinicopathological features of bladder cancer,TNFAIP3 was negatively correlated with pathological grade,degree of invasiveness and lymph node metastasis,but its role in renal cell carcinoma remains to be elucidated.In view of the above,the aim of this study was to investigate the expression of TNFAIP3 in ccRCC and to analyse the correlation between its expression and the clinicopathological characteristics of patients.Method1.Using the dynamic analysis of gene expression data 2(Gene expression profiling interactive analysis2,GEPIA2)database analysis TNFAIP3 differentially expressed in ccRCC tissues and normal renal tissue.2.In this study,97 cases of ccRCC tissues and corresponding paracancer normal kidney tissues with complete clinical data were collected.Immunohistochemical EnVision two-step method was used to detect the expression of TNFAIP3 in ccRCC tissues and corresponding paracancer normal kidney tissues.3.The number of cases(n)and expression rate(%)of ccRCC tissues and adjacent normal tissues in each group were counted,immunohistochemical score using mean ±standard deviation((?)±s)expressed,analysis TNFAIP3 with patient age,gender,the WHO/ISUP classification,the maximum diameter and TNM staging of tumor the clinical pathological characteristics.Result1.Analysis of GEPIA2 database showed that TNFAIP3 was highly expressed in ccRCC tissues compared with normal kidney tissues(P < 0.05).However,the Overall Survival(OS)and Disease-free survival(DFS)of ccRCC patients with high TNFAIP3 expression were significantly better than those with low TNFAIP3 expression(P < 0.05).2.Immunohistochemistry of TNFAIP3 showed that TNFAIP3 was expressed in the cell membrane and cytoplasm in ccRCC tissues,and the high expression rate in ccRCC tissues was significantly higher than that in adjacent normal kidney tissues(P < 0.05).3.The expression level of TNFAIP3 was correlated with clinical parameters of WHO/ISUP grade,maximum tumor diameter,TNM stage and lymph node metastasis in ccRCC tissue(P < 0.05),and high expression of TNFAIP3 suggested a good prognosis.ConclusionThe expression level of TNFAIP3 in ccRCC tissue was significantly increased,and the ccRCC patients with high expression of TNFAIP3 had better OS and DFS than those with low expression of TNFAIP3.This study revealed that TNFAIP3 is involved in the occurrence and development of ccRCC,which can provide a new direction and theoretical basis for the prognosis of ccRCC.Its role and molecular regulatory mechanism need to be further studied.