Research On The Role Of Wnt Pathway In The Occurrence And Development Of Ovarian Cancer

Epithelial ovarian cancer stands first in female gynaecological malignant tumor mortality rate.As early clinical symptoms aren’ t obvious,when it is diagnosed,patients are usually in the middle or late stage with poor prognosis and 5-year-survival rate is less than 30%.The standard therapy for ovarian cancer is tumor debulking and platinum-based chemotherapy.However,the effect of these treatments usually can’ t achieve its ideal effect.Ovarian cancer tumor recurrence and lymph node metastasis are the main factors that affect prognosis.In recent years,the research on ovarian cancer therapy has focused on both targeted drug therapy and pathogenesis.As the Wnt signaling pathway is well understood by people,many studies prove that irregular Wnt signaling pathwany will lead to abnormal transcription of target gene,which is closely related to the occurrence of cancer.In different tumor tissues,proteins of Wnt signaling pathway were highly expressed,and its high expression was closely related to tumor growth,lymph nodes metastasis,late clinical stage and poor prognostication.Wnt1 protein is one of the proteins of this pathway,regulates the classical Wnt/β-catenin pathway and PCP pathway.DKK1 protein acts as the Wnt signaling pathway inhibitor.In this paper,by using immunohistochemistry method,we detected the expression of Wnt1,DKK1 proteins in epithelial ovarian cancer,borderline ovarian tumors,benign ovarian tumors and normal ovarian tissue.The purpose is to explore the role of the Wnt signaling pathway in the development of ovarian cancer and to provide new ideas for the diagnosis,treatment and prognosis of ovarian cancer in the future.ObjectiveIn order to detect the expression of Wnt1 and DKK1 proteins in epithelial ovarian cancer,borderline ovary tumors,benign ovarian tumors and normal ovarian tissue and tell the relationship between the two proteins and clinical characteristics,such as the patients’ age,pathological type,lymph nodes and clinical stage.Methods1.The immunohistochemistry(IHC)was used to detect Wnt1 and DKK1 protein expression in four groups,41 cases of epithelial ovarian cancer,22 cases of normal ovarian tissue,10 cases of ovarian borderline tumors,and 7 cases of benign ovarian tumors.2.All data uses SPSS22.0 for statistical analysis,counting data uses Chi-square test and P<0.05 means statistically significant.Results1.Wnt1 protein expression in each groupIn the epithelial ovarian cancer group,the expression of Wnt1 protein showed a strong positive reaction(3+),and brown particles were seen in the cytoplasm and nucleus.Not only tumor cells were expressed,but weak positive expression was also seen in the extracellular matrix.The positive rate of protein expression was 63.4 %(26/41).In the borderline ovarian tumor group,positive(+)expression in local nucleus and cytoplasm could be seen,and the positive rate of protein expression was 10.0%(1/10).It is not expressed in the benign ovarian tumor group(-),but the extracellular matrix showed weak positive expression.The positive rate of protein expression was 0(0/7).In the control group,the spindle cells and the extracellular matrix showed positive expression,and the positive rate of protein expression was 54.5%(12/22).Among the four groups,the expression of Wnt1 protein in the epithelial ovarian cancer group was higher than the other three groups,and the difference was statistically significant(P<0.05).2.Relationship between Wnt1 protein expression and clinicopathological characteristics in epithelial ovarian cancer groupThe positive rate of Wnt1 protein expression in patients with lymph node metastasis was 90.9%(10/11),which was significantly higher than 47.8%(11/23)in patients without lymph node metastasis,and the difference was statistically significant(P<0.05).The later stage,the higher positive rate of Wnt1 protein expression.The positive rate of stage III+IV was 78.3%(18/23)significantly higher than that of stage I+II(44.4%),and the difference was statistically significant(P<0.05).There was no statistical difference in the positive rate of Wnt1 protein expression in the two groups of≥50 years old and <50 years old(P>0.05).Research results show that Wnt1 protein expression is related to lymph node metastasis and pathological stage,but not to age.3.DKK1 protein expression in each groupIn the immunohistochemical reaction,both the expression rate of DKK1 protein in each group and the position of positive expression was different.In the epithelial ovarian cancer group,DKK1 protein showed strong positive expression in the cytoplasm and nucleus.A few tumors showed no expression in tumor tissues,but positive expression in the extracellular matrix.The positive rate of protein expression in cytoplasm and nucleus was 46.3%(19/41).In the borderline ovarian tumor group,cytoplasmic expression was positive,and the positive expression rate was 30%(3/10).In the benign ovarian tumor group,there was positive expression in the cytoplasm,and the positive expression rate was 42.9%(3/7).In the control group,weak positive to positive expression can be seen around the spindle cells and follicles,and the positive expression rate was 45.5%(10/22).Although the positive rate of DKK1 protein expression in the epithelial ovarian cancer group was higher than that in other groups,it was not statistically significant(P>0.05).4.The relationship between the expression of DKK1 protein and clinicopathological characteristics in epithelial ovarian cancerIn the epithelial ovarian cancer group,the positive rate of protein expression in patients without lymph node metastasis was higher than that in patients with lymph node metastasis,but there was not statistically significant(P>0.05).The positive rate of clinical stage I and II was higher than that of III and IV,but there was not statistically significant(P>0.05).DKK1 protein is not related to age,lymph node metastasis or clinical stage(P>0.05).5.In the epithelial ovarian cancer group,some samples were expressed in the extracellular matrix.Wnt1 protein of 12 samples and DKK1 protein of 16 samples were expressed both intracellular and extracellular matrix or only in the extracellular matrix.Conclusions1.The expression rate of Wnt1 protein in epithelial ovarian cancer tissues is higher than that in borderline ovarian tumors,ovarian benign tumors and normal ovarian tissues.2.Wnt1 protein expression is related to lymph node metastasis and tumor stage of epithelial ovarian cancer.3.There is no difference in the positive expression rate of DKK1 in epithelial ovarian cancer and normal ovarian tissues.4.Wnt1 protein and DKK1 protein are expressed in the extracellular matrix,and further research is needed to study the expression in extracellular matrix.