Prognostic implication of forkhead box protein O1 (FOXO1) and paired box gene 3 (PAX3) in epithelial ovarian cancer.

Abstract

61 Background: Transcriptional factor, Forkhead box protein O1 (FOXO1) has been reported to play an imported role in human cancer, but the role in epithelial ovarian cancer (EOC) has not yet been clarified. Here, we evaluatedthe expression and clinical significance of FOXO1 in EOC. Methods: Immunohistochemical analyses of FOXO1 and PAX3 in 212 in EOCs, 57 borderline ovarian tumors and 153 benign epithelial ovarian tumors and 79 nonadjacent normal epithelial tissues were performed using tissue microarray analysis. The data were compared with clinicopathological variables including the survival of EOC patients. Also, the effect of FOXO1 on cell growth were assessed in EOC cell lines. Results: The expressions of FOXO1 and PAX3 protein were significantly higher in EOC tissues than in nonadjacent normal epithelial tissues, benign tissues and borderline tumors respectively (all p< 0.001). Overexpression of FOXO1 was significantly associated with poor grade ( p = 0.004). FOXO1 expression showed trend of positive correlation with that of PAX3 in EOC tissues ( Spearman’s rho0.118, p= 0.149). Multivariate survival analysis revealed that the high expression of FOXO1 (hazard ratio = 2.74 [95% CI, 1.22–13.10], p = 0.001) could be an independent prognostic factor for overall survival. Most importantly, high expression of both FOXO1 and PAX3 showed high hazard ratio (hazard ratio = 5.53 [95% CI, 2.47–12.40], p< 0.001) for overall survival. In vitro result revealed that knockdown of FOXO1 was associated decreased cell viability and migration. Conclusions: This study reveals that high expression of FOXO1/PAX3 is an indicator of poor prognosis in EOC. Our results not only suggest the promising potential of FOXO1 and PAX3 as a prognostic and survival marker, but also warrant further studies on a possible link between the biological function of FOXO1 and PAX3 of EOC.