Expression Of Apaf-1,caspase-9 And P53 In Ovarian Serous Carcinoma And Their Clinical Significances

Ovarian malignant tumor is one of the major malignant tumors in female reproductive system,the incidence is second and the mortality rate among the top of the gynecology malignant tumor.Ovarian serous carcinoma(OSC)is the most common histological type of ovarian malignant tumors,accounts for about 40% of the ovarian malignant tumor.High recurrence rate and mortality and bad prognosis is its main characteristic,because of its early symptom is not obvious,so most of the patients are diagnosed with advanced symptoms.At present,the treatment of ovarian cancer is mainly based on surgery and chemotherapy.Although many means treatment to a certain extent,prolong the patient’s life,but the patient’s survival rate is also low.The drug resistance of ovarian cancer patients to chemotherapy drugs has become an obstacle to clinical treatment.So it is important to find effective early diagnosis and treatment.Studies have shown that the occurrence and development of ovarian serous carcinoma is a process of multiple genes involved in the development of multiple stages,including abnormal cell apoptosis,growth factor and its receptor interaction and so on.And apoptosis is the focus of recent research.Apaf-1 is a multifunctional domain of the adaptor protein.Its function involves cell apoptosis,proliferation and differentiation.A series of signal transduction cascades in the human body are targeted to Apaf-1 and apoptosis.Apaf-1 leads to cell apoptosis via mitochondrial mediated pathway,which is an important Pro-apoptotic factor in mitochondrial apoptosis pathway.and its abnormal expression is closely related to the occurrence and development of a variety of malignant tumors.Caspase is a family of cysteine aspartate specific proteases,the family is an important protein in recent years the study found that the execution of apoptosis,is the core mechanism of apoptosis.And the Caspase-9 is one of the factors inducing apoptosis,located in the upstream of Caspase cascade,which is one of the most important components of Caspase family.It is one of the key components in the lower expression of organization associated with the occurrence and development of a variety of tumors.P53 is one of the most widely studied tumor suppressor genes,and more than 50% of malignant tumors will be mutated.Its protein play an important role in blocking cell growth and differentiation,promoting cell apoptosis and so on.However,mutant p53 has lost the inhibitory effect on cell proliferation and inhibited cell apoptosis,lead to the occurrence of tumor.Objective:To investigate the expression of Apaf-1,Caspase-9 and p53 in OSC,to analyze the correlation between Apaf-1,Caspase-9 and p53 and clinicopathological features,and the correlation between Apaf-1,Caspase-9 and p53 expression in OSC.To explore the role of Apaf-1,Caspase-9 and p53 in the occurrence and development of OSC,and to provide more theoretical references for the occurrence and development of the disease and clinical specific targeted therapy.Methods:The expression of Apaf-1,Caspase-9 and p53 in 45 cases of OSC,60 cases of ovarian serous cystadenoma and 32 cases of ovarian borderline serous cystadenoma were detected by immunohistochemical EnVision method.The relationship between Apaf-1,Caspase-9,p53 and the age of OSC,pathological grade,tumor clinical stage and lymph node metastasis was analyzed.SPSS19.0 software for statistical analysis,the relationship of Apaf-1,Caspase-9 and p53 between the expression and clinicopathological factors of OSC by χ2 test.The correlation of Apaf-1,Caspase-9 and p53 expression in OSC was examined by Spearman consistency test,with P<0.05 for the difference was statistical significant.Results:1.Apaf-1 expression in ovarian serous cystadenomas,ovarian borderline serous cystadenomas and OSC were 75%(45/60),46.9%(15/32)and 24.4%(11/45).The expression of Apaf-1 in OSC was significantly lower than that in ovarian serous cystadenomas and ovarian borderline serous cystadenomas(P<0.05).The positive expression rates of Caspase-9 in ovarian serous cystadenomas,ovarian borderline serous cystadenomas and OSC were 83.3%(50/60),56.3%(18/32)and 28.9%(13/45).Caspase-9 in OSC was significantly lower than that in ovarian serous cystadenomas and ovarian borderline serous cystadenomas(P<0.05).p53 in OSC was 46.7%(21/45),was higher than that in ovarian serous cystadenomas 5%(3/60)and ovarian borderline serous cystadenomas 9.4%(3/32)(P<0.05).2.Apaf-1 was significantly correlated with pathological grade,clinical stage and lymph node metastasis(P<0.05),but not with age.Caspase-9 was associated with pathological grade,clinical stage and lymph node metastasis of OSC(P<0.05),but not with age of patients.p53 was correlated with the age of patients,pathological grade,the clinical stage of OSC and lymph node metastasis(P<0.05).3.There was a significantly correlation between Apaf-1 and Caspase-9 expresion in OSC(P<0.05).The expression of Apaf-1 and p53 were positively correlated in OSC(P<0.05).There was no correlation between Caspase-9 and p53 in OSC.Conclusion:Both Apaf-1 and Caspase-9 are simultaneous lowexpress in OSC.The positive expression rate of Apaf-1 and Caspase-9 in OSC was significantly lower than that of ovarian serous cystadenomas and ovarian borderline serous cystadenomas,p53 expression in OSC was higier than than of ovarian serous cystadenomas and ovarian borderline serous cystadenomas.Suggesting that three of them were involved in the occurrence and development.The expression of Apaf-1 and Caspase-9 in OSC was not associated with the age of patients.But both of them was correlated with pathological grade,clinical stage and lymph node metastasis.p53 was as associated with the age of patients,pathological grade,clinical stage and lymph node metastasis in OSC.Suggesting that both of them were involved in the metastasis and invasion of OSC.There was a positive correlation between Apaf-1 and Caspase-9 in OSC,suggesting that they play a synergistic role in inhibiting the occurrence and development of OSC.It is suggested that the combined detection of the two may play an important role in determining the development and prognosis of OSC.The expression of Apaf-1 and p53 was positively correlated in OSC,suggesting that the two may have some relevance in the process and may participate in the occurrence of OSC.But there was no correlation between Caspase-9 and p53 in OSC.