Ovarian cancers present a mild clinical course when diagnosed early but an aggressive pathway when diagnosed in the peri- and postmenopausal periods. However, the predictability of tumor progression is stochastic and is difficult to predict. In the present study, we hypothesized to examine the key pathways that are dysregulated to promote epithelial-mesenchymal transition in serous ovarian carcinoma. Examination of these steps would help to identify ascitic fluid with cells poised for metastasis or otherwise. We focused on examining the Akt2 expression, mainly because of its report as being overamplified in the aggressive variants of ovarian cancer, as well as TGFbeta-sensitivity of Akt2 that forms the key basis for metastasis initiation of most kinds of carcinoma. We obtained primary ovarian carcinoma samples as well as ascitic fluid and distantly metastatic ovarian carcinoma to examine the expression of Akt2. The results of the study demonstrated that in malignant exfoliated ovarian cancer cells, Smad4 expression was tremendously increased in the nuclei, suggesting nuclear translocation of Smad, which thereafter may have activated ZEB2, and thereafter genomically affected the expression of E-cadherin, myosin II, and vimentin, key components for initiating and sustaining metastasis. All of these may have been stimulated by increased cellular expression of Akt2 in metastatic variants of the serous ovarian carcinoma. The reliance on Akt2 and TGF beta signaling may also potentiate the case for Akt inhibitors or small molecule inhibitors of TGFbeta signaling like doxycycline as adjunct chemotherapy in serous ovarian carcinoma, especially the metastatic variants.

AimTo evaluate the expression and clinical significance of hepatoma-derived growth factor (HDGF) in epithelial ovarian cancer (EOC).BackgroundRecent studies have demonstrated that HDGF overexpression correlates to the progression and poor prognosis in several kinds of cancers. However, the clinical significance and prognostic value of HDGF in EOC have not been investigated.MethodsExpression of HDGF was visualized by immunohistology and then the cohort was divided into higher- and lower-expression groups. The correlation between HDGF and clinicopathologic factors was analyzed by χ2 test. The prognostic value of HDGF was assessed by univariate analysis with Kaplan–Meier method, and by multivariate analysis with Cox-regression model. With experiments in vitro, HDGF expression in ovarian cancer cell lines was detected by immunoblotting.ResultsHigher HDGF expression rate was 52.76% in EOC. HDGF expression was significantly associated with lymphatic metastasis (P=0.006). Higher HDGF expression was closely correlated to poorer 5-year overall survival rate with univariate analysis (P=0.003), and was identified as an independent prognostic factor with multivariate analysis (P=0.007). With experiments in vitro, HDGF was proved to exist in all ovarian cancer cell lines with different expression levels.ConclusionHDGF expression correlates to unfavorable prognosis and can be considered as an independent prognostic factor, indicating that HDGF may be a promising potential molecular drug target.