title: CDKN3 is an independent prognostic factor and promotes ovarian carcinoma cell proliferation in ovarian cancer.
abstract: Cyclin-dependent kinase inhibitor 3 (CDKN3) has been reported to promote tumor genesis. Since it is unclear whether CDKN3 participates in the development of epithelial ovarian cancer (EOC), this study assessed the association between CDKN3 expression and cell biological functions, and demonstrated the clinical significance and prognosis of CDKN3 in EOC. CDKN3 expression was evaluated in 97 cases of tumor tissue by immunohistochemistry and in 60 tissues by western blotting. The clinical correlation was analyzed by Kaplan-Meier method and Cox hazards model. The molecular functional roles of CDKN3 in ovarian cancer cell line OVCAR3 were examined by small interfering RNA-mediated depletion of the protein followed by analyses of cell proliferation and invasion. Twenty-three out of 30 (76.7%) human EOC tissues exhibited stronger levels of CDKN3 protein compared with 10 out of 30 (33.3%) human ovarian surface epithelial (HOSE) tissues. The mean level of CDKN3 expression in the EOC tissues was 3.35-fold that in the HOSE tissues. CDKN3 protein was found to be overexpressed in 68.0% of the EOC samples and was correlated with poor patient survival (P<0.05). Furthermore, expression of CDKN3 was significantly associated with FIGO stage, recurrence and residual tumor size (P<0.05), and the CDKN3 status was a significant prognostic factor for EOC patients (P=0.005). In addition, depletion of CDKN3 expression inhibited the growth and clonogenic potential of the OVCAR3 cell line. Our present research found that CDKN3 may play an important role in the development and proliferation of EOC. CDKN3 may be used as a novel tumor marker to predict the prognosis of EOC.
authors.affiliation: Department of Gynecology, The First Hospital of China Medical University, Shenyang 110001, P.R. China.
authors.forename: Tianren
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Gynecology, The First Hospital of China Medical University, Shenyang 110001, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xue
authors.affiliation: Department of Gynecology, The First Hospital of China Medical University, Shenyang 110001, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Gynecology, The First Hospital of China Medical University, Shenyang 110001, P.R. China.
authors.forename: Kejun
authors.initials: K
authors.lastname: Guo
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002277:Carcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D000077216:Carcinoma, Ovarian Epithelial; D049109:Cell Proliferation; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000378:metabolism*; D054637:Dual-Specificity Phosphatases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D014408:Biomarkers, Tumor; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; C084429:CDKN3 protein, human; D054637:Dual-Specificity Phosphatases