The Expression And Significance Of SMAD4and FBXO32in Epithelial Ovarian Cancer

Objective: Ovarian cancer is one of the most common malignancies infemale reproductive system. It is difficult for patients to detect for itsnon-obvious clinical symptoms in the early, and then it's easy totransfer and become a widely growth in the abdominal cavity and pelvic cavity.For lack of early specificity screening and diagnostic criteria, the vast majorityof patients accept their treatment when the cancer has reached an advancedstage, so the mortality rate is persistently high. With the standard andsystematic treatment, clinical five-year survival rate of ovarian cancer Phase Iand II is up to70%-80%, while clinical five-year survival rate of ovariancancer Phase III and IV is only about30%. The occurrence and developmentis a multi-layered complex process, which is caused by its complex structureand function, as well as a variety of external factors. The pathogenesis ofovarian cancer is still haunting us, so we need to make deep comprehensionand exploration from more points of view. SMAD4protein is one of theSmads protein family, is a tumor suppressor gene. In the inhibition of tumoroccurrence and development, SMAD4can interact with any protein of Smadsprotein family and bring a variety of biological effects, and it is a keymolecule in the central position of TGF-β/Smads signaling pathways. WhenSMAD4is in a non functional status, lose of expression or reduce the level,TGF-β/SMAD4signal conduct abnormally, thereby it contribute to infiltration,metastasis and seeding growth of tumor. FBXO32protein, a member of F-boxprotein family, is an important part of the SCF ubiquity-protein ligase. Thestudy found that FBXO32as a tumor suppressor gene played a very importantrole in the TGF-β signaling pathways, which is involved in biologicalprocesses of many malignant tumors, but the study of FBXO32specificpathogenesis is less at present. By measuring the expression level of SMAD4 and FBXO32protein in different ovarian tissue, our experiment investigatedthe clinical significance of SMAD4and FBXO32, which provided a newexperimental basis for the pathogenesis of epithelial ovarian cancer, earlydiagnosis, condition monitoring, targeted treatment and improved prognosis.Methods:In this study, with immunity-histochemistry SP method, we detectexpression of SMAD4and FBXO32in19cases of normal ovarian tissue,27cases of benign ovarian tumor and60cases of epithelial ovarian cancer tissue,and assess relationships among the two protein and various clinicopathologicalparameters of epithelial ovarian cancer in order to explore their clinicalsignificance. We make statistical analysis of data with statistical softwareSPSS13.0. When P <0.05, it is significant difference and the experiment hasits statistically significance.Results:1SMAD4and FBXO32mainly existed in the normal ovarian epitheliumand the cytoplasm of the benign ovarian tumor and epithelial ovariancarcinoma, less expressed in the cell nucleus and membrane.2The positive expression rate of SMAD4in the normal ovarian epitheliumwas68.4%(13/19). The positive expression rate of SMAD4in benign ovariantumor was63.0%(17/27). The two rates are significantly higher than thepositive expression rate38.3%(23/60) in epithelial ovarian cancer andstatistical analysis shows the difference is significant (P<0.05).3The comparison of SMAD4protein expression in epithelial ovarian cancerwith different amount of ascites shows that the positive expression rate57.6%(15/26) of the group in which ascites is less than1000ml was significantlyhigher than that ascites is larger than1000ml,23.5%(8/34). Statisticalanalysis shows the difference is significant (P<0.05). Comparing thehistological grade group of epithelial ovarian cancer, we found that thepositive expression rate (62.5%10/16) of well-differentiated ovariancarcinoma was significantly higher than the positive expression rate (29.5%13/44) of the poorly differentiated ovarian carcinoma. The statistical comparison shows difference is significant and the experiment has itsstatistically significance(P<0.05). The comparison of different FIGO clinical,surgical-pathological staging shows the positive expression rate (64.3%9/14)of early clinical epithelial ovarian cancer, called Phase I and II, is higher thanpositive expression rate of the advanced epithelial ovarian cancer (30.4%14/46), called Phase III and IV. And the statistical comparison tells thedifference is significant and the experiment has its statistically significance(P<0.05). Using statistical analysis tools, we compare the positiveexpression rates of epithelial ovarian cancer with different pathological typesand the result is P>0.05. That means there is no significant difference instatistics.4The positive expression rate of FBXO32in the normal ovarian epitheliumwas84.2%(16/19). The positive expression rate of SMAD4in benign ovariantumor was70.3%(19/27). The two rates are significantly higher than thepositive expression rate45.0%(27/60) in epithelial ovarian cancer andstatistical analysis shows the difference is significant.5The comparison of FBXO32protein expression in epithelial ovariancancer with different amount of ascites shows that the positive expression rate73.1%(19/26) of the group in which ascites is less than1000ml wassignificantly higher than that ascites is larger than1000ml,23.5%(8/34).Statistical analysis shows the difference is significant (P<0.05). Comparingthe histological grade group of ovarian cancer, we found that the positiveexpression rate (68.8%11/16) of well-differentiated ovarian carcinoma wassignificantly higher than the positive expression rate (36.4%16/44) of thepoorly differentiated ovarian carcinoma. The statistical comparison showsdifference is significant and the experiment has its statistically significance(P<0.05). The comparison of different FIGO clinical, surgical-pathologicalstaging shows the positive expression rate (71.4%10/14) of early clinicalovarian cancer, called Phase I and II, is higher than positive expression rate ofthe advanced epithelial ovarian cancer (37.0%17/46), called Phase III and IV.And the statistical comparison tells the difference is significant and the experiment has its statistically significance(P<0.05). Using statistical analysistools, we compare the positive expression rates of ovarian cancer withdifferent pathological types and the result is P>0.05. That means there is nosignificant difference in statistics.Conclusion:1SMAD4and FBXO32protein were highly expressed in the epithelial cellsof normal ovarian tissue and benign ovarian tumor, while showed lowexpression in epithelial ovarian cancer. This tells us that missing expression ofSMAD4and FBXO32protein may lead to the interruption of TGF-β signalingpathway, thereby contributing to the occurrence of epithelial ovarian cancer.2The expression of SMAD4and FBXO32in epithelial ovarian cancer iscorrelated to the amount of ascites in epithelial ovarian cancer, histologicalgrade and FIGO clinical, surgical-pathologic stage, while it isn't correlated tothe pathological types. This suggests that SMAD4and FBXO32protein maybe involved in inhibiting development, infiltration, metastasis and seedinggrowth of epithelial ovarian cancer.3The expression of SMAD4and FBXO32protein in normal ovarian tissue,benign ovarian tumors and epithelial ovarian cancer suggests that SMAD4andFBXO32protein may become the new screening indicator in the earlyepithelial ovarian cancer. They can be used to improve the rate of earlydiagnosis of epithelial ovarian cancer and5-year survival rate. SMAD4andFBXO32protein can improve efficacy by making targeted treatment and alsoimprove the prognosis.