Association of forkhead box protein O1 and paired box gene 3 overexpression with prognosis in patients with cervical cancer.
e14519 Background: Transcriptional factor FOXO1and PAX3 has been reported to play an imported role in human cancer, but the role in cervical cancer has not yet been clarified. Here, we evaluated the functional role of FOXO1 with cervical cancer cells and the expression together with clinical significance of FOXO1 and PAX3 among cervical lesions was investigated. Methods: In vitro assessment of cell functions by cell viably assay, cell migration and invasion assay was evaluated using FOXO1 knockdown cervical cancer cell lines. Immuno-histochemical (IHC) staining analyses of FOXO1 and PAX3 were performed with tissue microarray (TMA) consisting of 209 cervical cancers, 366 high grade cervical intraepithelial neoplasias (CIN), 130 low grade CIN and 328 matched nonadjacent normal cervical epithelial tissues. The clinical significance was investigated by comparing the data with various clinicopathologic characteristics, including survival in cervical cancer. Results: In vitro result revealed that knockdown of FOXO1 was associated decreased cell viability ( p< 0.001), migration ( p< 0.001) and invasion ( p< 0.05) supporting the oncogenic role of FOXO1 in cervical cancer. FOXO1 and PAX3 expression was significantly higher in CIN (both p< 0.001) and cancer tissue (both p< 0.001) than in normal tissue. FOXO1 expression showed significant correlation with PAX3 (Spearman’s rho = 0.377, p< 0.001) in a cervical cancer. Multivariate analysis indicates that FOXO1 expression (hazard ratio = 4.01 [95% CI, 1.22–13.10], p= 0.021) and advanced FIGO stage (hazard ratio = 3.89 [95% CI, 1.35–11.19], p= 0.012) were independent prognostic factor on overall survival. Conclusions: This study reveals the association between FOXO1 and PAX3 expression with clinicopathologic variables, including survival of cervical cancer patients. Our results not only suggest the promising potential of FOXO1 as a prognostic and survival marker, but also warrant further studies on a possible link between the biological function of FOXO1 and the pathogenesis of cervical cancer.