The Expression And Clinical Significance Of Smad4Signaling Pathway Protein And Cortactin Protein In Ovarian Neoplasms

ObjectiveThis subject aims to detect the expression of Smad4、Cortactin gene and Smad4、Cortactin protein in epithelial ovarian tumors，and study its relationship with epithelialovarian cancer clinical and pathological variables, and the correlationship of expression ofSmad4and Cortactin, further to explore the role of Smad4signaling pathway in theepithelial ovarian cancer development process, as well as the impact of Smad4for cellmovement, provide the basis for prognosis and provide new targets for clinical treatment.MethodsIn this study use epithelial ovarian cancer as the research object，benign ovarianepithelial tumor and normal ovarian tissue as control group, using real-time fluorescencequantitative PCR (Method of Real-time quantitative reverse transcription polymerase chainreaction） to detect the expression of Smad4and Cortactin mRNA；immunohistochemistry SP three step method to detect the expression of Smad4protein andCortactin protein in different ovarian tissues.Results1．The relative content of Smad4mRNA in epithelial ovarian cancer is less thanbenign ovarian tumors and normal controls (P<0.05), The expression of Smad4mRNA inOvarian benign tumor tissues is5.75times in epithelial ovarian carcinoma.The expressionof Smad4mRNA were negatively correlated with ovarian cancer histological grade,FIGO stage, lymph node metastasis and ascites（P﹤0.05）.2．The relative content of CortactinmRNA in epithelial ovarian cancer is higher thanbenign ovarian tumors and normal controls (P<0.05); The expression of CortactinmRNA isrelated with ovarian cancer histological grade, FIGO staging（P﹤0.05）, not related withage、 lymphnode metastases and ascites (P>0.05). 3．Smad4Protein was mainly localized in the cytoplasm of tumor cells, partly locatedin the nucleus, showing a brown or tan particles. The positive expression of Smad4proteinin epithelial ovarian carcinoma was44.00%, weakly positively.And the positive expressionrate of Smad4protein in benign ovarian tumor and normal ovarian tissues is70.00%,strongly positive; The positive expression of Smad4Protein is related with histologic grade,clinical staging, lymph node metastasis of ovarian cancer and ascites (P<0.05).4．Cortactin Protein located in the cytoplasm and the cell membranes of the tumorcells, partly located in the nucleus. The positive expression rate of Cortactin protein inepithelial ovarian carcinoma is73.30%,mostly expressing strongly positive; The positiveexpression rate of Cortactin Protein in benign ovarian tumors and normal control tissues isless than25%, weakly positive; The expression of Cortactin Protein in epithelial ovariancancer is only related with histological grade（P﹤0.05）, not related with FIGO stage,lymph node metastasis, ascites and age(P>0.05).5．It showed according to SPearman correlation analysis: mRNA expression betweenSmad4and Cortactin showed moderate negative correlation in epithelial ovarian carcinoma(r=-0.541, P=0.005); while it was highly linear negative correlation between theexpression of Smad4and Cortactin the organization (r=-0.738, P=0.000).6．Epithelial ovarian cancer the positive of Smad4Protein average survival time was40.6±4.2months (95%CI,35.3-43.0months),ones of negative expression mean survivaltime was26.1±5.3months (95%CI,24.7-30.6months), the difference was statisticallysignificant (P=0.026), the Positive expression of Cortactin average survival time was19.5±1.2months (95%CI,14.6-21.4months), negative expression mean survival time was34.5±4.3months (95%CI,22.1-25.9months), the difference was statistically significant(P=0.017).7．Univariate analysis showed that: the positive expression of Smad4representsignificant survival advantage than those with negative exPression in ePithelial ovariancancer patients (x2=4.944, P=0.026). And the negative expression of Cortactinrepresenting a significant survival advantage than the positive expression (x2=5.739, P=0.017). COX regression model for multivariate analysis, both of which are independentprognostic factors of epithelial ovarian cancer, which smad4negative expression:P=0.001RR=5.412(95%CI,2.719-6.112), Cortactin exPression: P=0.001RR=6.452(95%CI,2.289-7.512). Conclusions1．Smad4mRNA and Protein expression exists deficiency in epithelial ovariancancer,the loss expression of Smad4protein in epithelial ovarian tumors related withFIGO clinical stage, histological grade, lymph node metastasis and the presence of ascites.Univariate analysis showed positive expression of Smad4have a significant survivaladvantage, multivariate analysis showed Smad4expression as an independent prognosticfactor. It showed that Smad4is key aspects of TGF-β signaling pathway.Its loss ofexpression may play a role in promoting the malignant progression of ovarian cancer,Smad4negative expression means a poor prognosis.2．Cortactin mRNA and protein expression in epithelial ovarian cancer tissues wassignificantly higher than benign ovarian tumors, mRNA expression of Cortactin associatedwith histological grade and FIGO stage of ovarian cancer, while the expression ofCortactin protein only related to histological grade of ovarian cancer. Univariate analysisshowed negative expression of Cortactin have a significant survival advantage,multivariate analysis showed that Cortactin expression as an independent prognostic factor.Description the poorer tumor cell differentiation, the stronger cell movement activity is, asan important cytoskeletal Protein, Cortactin regulated exPression and poor prognosis ofovarian cancer are closely related.3．The mRNA expression between Smad4and Cortactin has moderate negativecorrelation epithelial ovarian cancer (r=-0.541, P=0.005); and the protein expressionbetween Smad4and Cortactin was highly negatively correlated (r=-0.738, P=0.000).High correlation between Smad4and Cortactin show that: TGF-β signaling Pathway mayregulate cytoskeletal proteins through Smad4, Cortactin may be an important downstreamtarget genes of Smad4pathway,tumor cells regulate the ability of cell motility throughSmad4-Cortactin pathway, thereby affecting the invasion and metastasis of tumor cells.Smad4-Cortactin cell motility pathway may have potential biological therapeutic value.