Expression Of YAP And Cyclin E In Ovarian Serous Carcinoma And Their Correlation With Tumor Associated Macrophage

Purpose Studying the expression of Hippo pathway related protein and its downstream regulator Cyclin E in the tissue of ovarian serous carcinoma(OSC).To analyze the correlation between the expression of YAP and Cyclin E and the clinicopathological indexes of the two proteins.We also explored the effect of YAP on the prognosis of the patients.Analyzing the expression of YAP and the distribution of tumor-associated macrophage(TAM)in OSC,and to explore the effect of YAP positive tumor cells on the tumor microenvironment,especially the immune factors.Method 1.Collecting 96 cases of OSC,10 cases of oviduct epithelial tissue,20 cases of serous cystadenoma and 20 serous borderline cystadenoma(SBT)with its clinical information.Immunohistochemical method PV-6000 was used to detect the expression of YAP and Cyclin E.The statistical software SPSS 19.0 was used to analyze the differences in the expression of YAP and Cyclin E among different tissues,and the correlation between the expression level of YAP and Cyclin E and the clinicopathological indexes.Survival analysis of OSC patients with different YAP levels was performed by Kaplan-Meier and Cox regression analysis 2.Immunohistochemical was used to classify the TAM in 96 OSC tissues.CD68 labeled all macrophages,CD11 b labeled M1 macrophages,and CD206 labeled M2 type macrophages.Observing the effect of YAP protein expression on the type and distribution of TAM in tumor tissues.Result Part one: 1.The expression rates of YAP in OSC,normal tubal epithelium,serous cystadenoma and SBT tissues were 68.75%(66/96),10%(1/10),15%(3/20)and 20%(4/20).The expression rates of Cyclin E in these tissues were 72.91(70/96),0%(0/10),0%(0/20)and 20%(4/20),respectively.The expression level of YAP and Cyclin E in OSC was significantly higher than that in normal oviduct epithelium,serous cystadenoma and SBT,and the difference was statistically significant.2.In OSC,the expression of YAP was significantly correlated with age,pathological grade and clinical stage(P < 0.05).There was no significant difference in the diameter of the tumor(P > 0.05),and the expression of Cyclin E in high grade OSC had a tendency to rise,but there was no significant difference(P > 0.05).The expression of Cyclin E was no significant difference in age of patients,tumor diameter or clinical stage(P > 0.05).3.In OSC,normal tubal epithelium,serous cystadenoma and SBT,the expression of YAP and Cyclin E showed significant positive correlation.In YAP positive cases,the positive rate of Cyclin E increased significantly,while the Cyclin E positive rate of YAP negative patients decreased significantly.4.Prognosis analysis showed that the overall survival(OS)and disease-free survival(DFS)in patients with high expression of YAP were significantly shorter than those with low expression of YAP patients(P < 0.05).Single factor Cox regression analysis showed that YAP protein was a risk factor for OS and DFS in OSC patients,and the multifactor Cox regression model showed that the high expression of YAP protein was an independent risk factor for DFS in OSC patients(P < 0.05).Part two: The expression of YAP is positively correlated with M2 macrophages in OSC tumor tissues.Immunohistochemical showed that there was no significant difference between the expression of YAP and the expression of CD68 and CD11b(P > 0.05),but there was a significant positive correlation between the expression of YAP and the CD206 positive macrophages(P < 0.05).The aggregation of CD206 positive macrophages was observed in tumor with high expression of YAP.Conclusion The expression of YAP protein in OSC patients is significantly increased,Hippo pathway is activated,which directly upsets the expression of downstream proliferation regulator Cyclin E,promoting the occurrence of OSC and the proliferation of tumor cells.The expression of YAP and Cyclin E is low in normal tissues,and there is a significant difference in the expression of different types of tumor.Immunohistochemical examination combined with the detection of YAP and Cyclin E expression is helpful to the differential diagnosis of benign and malignant ovarian serous tumors.In addition,?50 years old,high pathological grade and high clinical stage(III or IV stage)were relatively high expression of YAP.On the contrary,YAP was relatively <50 years old,low pathological grade and low clinical stage(I or II stage).More importantly,patients with high YAP expression have poorer prognosis.YAP protein is an independent risk factor for prognosis in OSC patients.High expression of YAP promotes the recruitment of M2 type macrophages in the tumor microenvironment,and further promotes the survival,growth and angiogenesis of tumor tissue,and provides a microenvironment for the survival of tumor cells.Therefore,YAP protein detection is helpful to the differential diagnosis of ovarian tumor,and it is involved in the research of the mechanism of tumor development.It can provide important basis for YAP to be a new target of OSC treatment and provide a new diagnosis and treatment idea for clinical immunotherapy.