The Expression And Clinical Significance Of P-AKT?FOXO3a And Bim In Epithelial Ovarian Cancer

Ovarian cancer,cervical cancer and endometrial carcinoma are the three malignant tumors about female reproductive system.Though ovarian cancer,s incidence rate is the lowest,1/2500 in female who are beyond 50 years old,it has the highest malignancy and death rate,and ovarian cancer is one of the most invasive malignant tumors.The new diagnosed ovarian cancer patients every year around the world are 240 thousand,and 150 thousand die.The new diagnosed ovarian cancer patients in 2015 in Chinese mainland are 52 thousand,and 23 thousand die.Since ovarian cancer is lack of effective early diagnosis index,the disease is always diagnosed on moderate or late stage,including 70%-75% patients are diagnosed on III or IV stage,and appear advanced symptoms,such as ascites,cachexia and ileus etc.and is easy to relapse.At present treating the ovarian cancer patients is surgery and many courses of chemotherapy,though through this combination therapy can improve the life quality of many patients,but the ending is always not optimistic,and 5-year survival rate is still low grade,just around 30%.The ovarian malignant tumor is to be divided three classes,ovarian epithelial tumor,ovarian sex cord stromal tumor and ovarian germ cell tumor,and the epithelial ovarian cancer is 75%~90%.Although at present many researches from domestic and foreign about ovarian cancer have been published,its etiology and pathogenesis are not clear yet.To explore the mechanism of development and progression of EOC,and research the peculiar,sensitive serum maker or other tissues and effective therapy target,are always the most important aim in the ovarian cancer field.Looking for new marker to improve the specificity and sensitivity of early EOC,s diagnosis and prognosis has no time to delay.Investigating relevant markers can not only provide guidance for preventing EOC,but also provide direction to targeted therapy.FOXO3a is one important transcription factor and cancer suppressor gene,existing in human tissues widely and expressing many important physiological functions.The newest researches from domestic and foreign find that the expression of FOXO3 a in gastric cancer?liver cancer?breast cancer?prostate cancer and etc.is downgrade,and related to tumor malignancy.FOXO3 a is existing in PI3K/AKT pathway,which is known to be one of the most important pathways controlling proliferation,differentiation and apoptosis.AKT is a cancer kinase which is the first verified to make FOXO3 a phosphorylation.When excessive nutrition and others attack cells,AKT is phosphorylated and become p-AKT,from cytoplasm into karyon,combined with FOXO3 a,then FOXO3 a is phosphorylated and this weaken its combining with DNA,but enhance its combining with 14-3-3 protein,from karyon into cytoplasm,hydrolyzed by protease and lose activity.FOXO3 a has many target genes,such as Bim,belong to Bcl-2 family,which can make cell apoptosis.Researches find that FOXO3 a inactivation happen in protein modification level,which is absent in EOC.So,the author study the expression of p-AKT?FOXO3a and Bim in EOC,and discuss their relationship to hope to provide new thoughts?theoretical evidence for target therapy and prognosis evaluation of EOC.ObjectiveTo investigate the expression of p-AKT?FOXO3a and Bim in mRNA and protein level in normal?benign and malignant ovarian epithelial tissues,and analyze the relationship among them in protein level in EOC.And discussing the important value of FOXO3 a for EOC,therapy and prognosis.Materials and methods1.The normal tissues are 25 cases,and come from benign uterine disease,such as the age is beyond 50 years old,and have been diagnosed uterine myoma ?endometriosis etc.and the adnexa have been surgical resected;the benign are 21 cases,and the malignant tissues are 43 cases,all come from epithelial ovarian neoplasms tissues which haven,t been chemoradiotherapied and other therapy before surgery.All the specimens are verified by surgery and pathology and get the agreement of patients and the Ethics Committee.2.Methods qRT-PCR method was used to detect the mRNA expression of FOXO3 a and Bim in 89 cases of epithelial ovarian tissues.Immunohistochemical method was used to detect the protein expression of p-AKT?FOXO3a and Bim in 89 cases of epithelial ovarian tissues.3.Statistics approach Dealing with the data by using SPSS21.0.The mRNA expression was evaluated by M(P25~P75),and use rank sum test to compare the expression in three different groups.Using Chi-square to compare the enumeration data.And through Spearman rank correlation to analyze the correlation of the three factors.Significant level ?=0.05,the comparision among three groups,significant level ??=?/3=0.0167.Results1.the expression quantity contrast of FOXO3a?Bim mRNA in three tissues The expression quantity of FOXO3 a mRNA in normal?benign?malignant group is 0.753(0.350,1.500)?0.563(0.450,1.875)?0.883(0.438,1.938),and the contrast among three groups have no statistical difference(P>0.05).Bim mRNA is 1.585(0.625,2.500)0.285(0.236,2.376)?0.060(0.029,0.413),and the contrast have statistical significance(P<0.05).2.the protein expression contrast of p-AKT?FOXO3a and Bim in three tissues The expressional level of p-AKT protein in the normal group is low expression,and in the malignant group is high expression,and the difference is statistically significant(P<0.0167);FOXO3a and Bim proteins in the normal group are high expression,and in the malignant group are low expression,and the difference is statistically significant(P<0.0167).3.the correlation between clinical pathological features and p-AKT?FOXO3a and Bim protein in EOC The expressional level of p-AKT?FOXO3a and Bim protein associate with the histological grade of EOC(P<0.05),and have no obvious correlation with the histological type,patient age,clinical stage,and lymph node metastasis(P>0.05).4.the correlation analysis of p-AKT?FOXO3a and Bim protein in EOC Through the Spearman test,the correlation between FOXO3 a protein and p-AKT protein is negative(r=-0.584,P<0.05),and positive correlation between FOXO3 a protein and Bim protein(r=0.437,P<0.05).Conclusions1.The FOXO3 a may play a role in EOC,occurrence and development,and it lose activity may happen in the protein modification level after translation.The Bim may also influence the occurrence and development of EOC,and it lose activity may happen in the transcriptional level.2.The p-AKT protein in malignant epethelial ovarian tissues is high expression,suggesting that it may participate in the occurrence and development of EOC.3.The p-AKT?FOXO3a and Bim protein are related with the differentiated degree of EOC,suggesting that they may become the index of predicting the differentiated degree of tumor cells.4.In EOC,FOXO3 a has negative correlation with p-AKT,and positive correlation with Bim,suggesting that they may together regulate the occurrence and development of EOC through some mechanism.