The Relationship Between The Expression Of Hippo-YAP1 And SOX2 With The Epithelial Ovarian Cancer

Objective:To investigate the expression of Large tumor suppressor2(LATS2),Yes-associated protein1(YAP1), Yes-associated protein1(phosphorylated)(YAP1(phospho)) and SRY related high mobility group box 2(SOX2) in epithelial ovarian carcinoma(EOC) and the relationship between the expression and clinical parameters of epithelial ovarian cancer and to evaluate their roles on the origin and progression of epithelial ovarian cancer.Methods:We examined the expression of LATS2,YAP1, YAP1(phospho) and SOX2 in86 cases of ovarian carcinoma, and 20 cases of normal ovarian tissue by SP immunohistochemical technique. We established the epithelial ovarian cancer cell lines which stable transfected with SOX2 gene; and detected the expression of SOX2 and YAP1 in the stable cell lines by Western-blot; and detected the migration ability of cells which are over expressed with SOX2 by Wound healing assay.Results:The positive expression rate of LATS2 in epithelial ovarian cancer was significantly lower than that in normal ovarian tissues(p<0.01); The ratios of YAP1,YAP1(phospho) and SOX2 over-expression in ovarian cancer were much higher than that in normal ovarian tissues(p < 0.01). The positive expression rate of YAP1(phospho) in normal ovarian tissues was significantly higher than that of YAP1(p<0.05). In epithelial ovarian carcinoma tissues, the ratio of YAP1 positive-expression had no difference with that of YAP1(phospho) positive-expression(p>0.05). The high expression rate of YAP1 in the advanced stage of ovarian cancer was significantly higher than that in the early stage of ovarian cancer, while the high expression rate of YAP1(phospho) in the advanced stage of ovarian cancer was significantly lower than that in the early stage of ovarian cancer(p < 0.01). The expression of YAP1 revealed significant relationship to the chemotherapy resistance,metastasis, FIGO stage, and tissue differentiation(p<0.01), but had nothing to do with age. The patients with YAP1 over-expression had shorter life time than those without YAP1 over-expression(p<0.01). Spearman correlation analysis showed that YAP1 over-expression was positively correlated with SOX2 over-expression(r=0.635,p<0.01). The expression of YAP1 protein was also significantly up-regulated in the cells which were up-regulated by the expression of SOX2.(p<0.05), The increase of SOX2 expression makes the cell migration ability significantly improved(p<0.05).Conclusion:Down-regulation of LATS2 expression with over-expression of YAP1 and SOX2 is closely related to the origin and progression of epithelial ovarian cancer.YAP1 and SOX2 can be used as a marker of poor prognosis in epithelial ovarian cancer. The high expression of YAP1(phospho) indicates that the epithelial ovarian cancer is in the early stage. SOX2 may regulate the migration of epithelial ovarian cancer cells through its positive regulation of the expression of YAP1, to promote the metastasis of epithelial ovarian cancer.