| Bladder Urothelial carcinoma,BUC is the main histological type of Bladder cancer.With its multiple lesions,easy recurrence,easy metastasis and easy to produce drug resistance,it has become a hotspot field in the field of biomedical research.There are many studies on the mechanism of the occurrence and development of bladder urothelial carcinoma,but no definite conclusion has been reached.It is generally believed that tumor growth and differentiation is a complex multistage process in which multiple genes and various factors mediate participation.The invasion and metastasis of cancer cells involves the changes of DNA,RNA,protein levels and regulatory mechanisms.The abnormality of apoptosis is closely related to the occurrence and development of cancer.Therefore,apoptosis and its mechanism have always been one of the hotspots in the field of cancer research.Caspase(Cysteinyl aspartate specific proteinase)is a family of cysteine aspartate specific proteases that are key enzymes in the regulation of apoptosis and are central to apoptosis.Caspase-3 is located downstream of the Caspase family's apoptotic response,located at the intersection of mitochondrial and death receptor pathways and is an important effector molecule for apoptosis.The family members of the inhibitor of apoptosis pretein(IAPs)are the endogenous Caspase inhibitors.XIAP plays a role in the mitochondria both upstream and downstream,and its function in inhibiting apoptosis is mainly achieved by inhibiting the Caspase family pathway.Apoptotic protease activating factor-1(Apaf-1)is a multifunctional domain adapter protein.Its function involves many aspects of apoptosis,proliferation and differentiation.A series of signal transduction cascades in human body are all regulated by Apaf-1 as the center.Apaf-1 induces apoptosis through the mitochondrial pathway and is a key pro-apoptotic factor in the mitochondria-mediated pathway.There are many researches on the role of Caspase-3 in tumor develop-ment.It was found that the expression of XIAP was up-regulated in various tumors,and is related to the main features of tumor cell apoptosis,development and metastasis.The abnormal expression of apaf-1 is closely related to the occurrence and development of various malignant tumors.However,studies on the expression and clinicopathological significance of XIAP,Apaf-1 and Caspase-3 in BUC have not been reported in the literature.The expression and significance of apoptosis-related factors XIAP,Apaf-1 and Caspase-3 in bladder urothelial carcinoma,and explored the process of apoptosis mitochondrial pathway in the development of bladder urothelial carcinoma.The possible role and its correlation,in order to provide more theoretical references for the clinical diagnosis,treatment and prognosis of bladder urothelial carcinoma.Objective:In this study,immunohistochemistry was used to detect the expression of XIAP,Apaf-1 and Caspase-3 in bladder urothelial carcinoma at the protein level.Analysis of the relationship between the three and clinical pathological factors in BUC and XIAP,Apaf-1 and Caspase-3 protein expression.To explore the role of XIAP,Apaf-1 and Caspase-3 in the development of BUC and their significance in the joint detection of the three.Provide more theoretical reference for the diagnosis,treatment and prognosis of clinical BUC.Methods:The expressions of XIAP,Apaf-1 and Caspase-3 in 68 cases of bladder urothelial carcinoma and 21 cases of normal bladder tissues were detected by immunohistochemical EnVision method.To analyze the correlation between the expression of XIAP,Apaf-1 and Caspase-3 and the clinicopathological features of bladder urothelial carcinoma,including the age,tumor size,histological grade,pathological stage and lymph node metastasis and other pathological factors.SPSS19.0 software was used for statistical analysis.The expression of XIAP,Apaf-1 and Caspase-3 and their relationship with clinicopathological factors of BUC were analyzed by?~2 test.The correlation between the three expressions was tested by Spearman's consistency test.The difference in P<0.05 was statistically significant.Result:1.Positive immunoreaction of XIAP,Apaf-1 and Caspase-3 were located in cytoplasm and/or nucleus.In 68 cases of bladder urothelial carcinoma tissues,the positive expressions rate of XIAP,Apaf-1 and Caspase-3 were80.1%(55/68),25.0%(17/68)and 39.7%(27/68).The positive expressions rate of XIAP,Apaf-1 and Caspase-3 in 21 cases of normal bladder tissues were19.0%(4/21),76.2%(16/21)and 71.4%(15/21).The expression of XIAP was higher in bladder urothelial carcinoma tissues than in normal bladder tissues(P<0.05).The expressions of Apaf-1 and Caspase-3 in bladder urothelial carcinoma tissues were lower than that in normal bladder tissues(P<0.05).2.The high expression of XIAP in bladder urothelial carcinoma was associated with histological grade,pathological stage and lymph node metastasis(P<0.05),but there was no significant correlation with age and tumor size of patients with bladder urothelial carcinoma(P>0.05)Low expression of Apaf-1 was associated with histological grade,pathological stage and lymph node metastasis of bladder urothelial carcinoma(P<0.05),and there was no significant correlation with age and tumor size of patients with bladder urothelial carcinoma(P>0.05).Like Apaf-1,the low expression of Caspase-3 was also closely related to histological grade,pathological stage and lymph node metastasis of bladder urothelial carcinoma(P<0.05),and has no significant correlation with the age and tumor size of patients with bladder urothelial carcinoma(P>0.05).3.There was a significantly negatively correlation between Apaf-1 and XIAP in bladder urothelial carcinoma(P<0.05).The expression of Apaf-1 and Caspase-3 was positively correlated(P<0.05),and the expression of XIAP and Caspase-3 was negatively correlated in bladder urothelial carcinoma(P<0.05).Conclusion:1.XIAP is highly expressed in bladder urothelial carcinoma,while the positive expression rate of Apaf-1 and Caspase-3 in bladder urothelial carcinoma is lower than that in normal bladder tissue,showing low expression,suggesting XIAP,Apaf-1 and Caspase-3 plays a role in the process of bladder urothelial carcinoma.2.The expressions of XIAP,apaf-1 and caspase-3 are closely related to the histological grading,pathological staging and lymph node metastasis of bladder urothelial carcinoma,which may be one of the important factors in the invasion and metastasis of bladder urothelial carcinoma.3.There was a negative correlation between the expression of XIAP and Apaf-1 in bladder urothelial carcinoma,and a negative correlation between the expression of XIAP and Caspase-3,while the expression of Apaf-1 and Caspase-3 was positively correlated.The interaction of these three factors may be one of the important factors for the occurrence and development of bladder urothelial carcinoma. |
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