Overexpression of kinesin family member 20A is associated with unfavorable clinical outcome and tumor progression in epithelial ovarian cancer

Han Li,1,* Weijing Zhang,1,* Xiaoying Sun,1,* Jueming Chen,1 Yue Li,1 Chunhao Niu,2 Benke Xu,3 Yanna Zhang1 1Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; 2Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, Guangdong, China; 3Department of Anatomy, Medical School of Yangtze University, Jingzhou, China *These authors contributed equally to this work Background: KIF20A plays an indispensable role in cytokinesis regulation, which is important for tumor proliferation and growth. Recently, the oncogenic role of KIF20A has been well documented in several cancers. However, its clinical role in epithelial ovarian cancer (EOC) remains not reported yet. We investigated its expression and its role in promoting invasion and chemoresistance in EOC cells.Patients and methods: KIF20A transcription and translation levels were investigated in normal ovarian epithelial cell, ovarian cancer cells, and 10 pairs of fresh EOC tissues and adjacent normal ovarian tissues by real-time quantitative polymerase chain reaction and Western blots. Moreover, KIF20A protein level was also examined by immunohistochemistry in 150 EOC tissues. The correlation between KIF20A expression and clinical variables was analyzed by statistical methods. We also used wound healing assay, transwell assay MTT, and Annexin V/PI to explore KIF20A functions.Results: KIF20A expression was obviously elevated at both mRNA and protein levels in EOC cell lines and clinical cancer tissues compared with normal ovarian epithelial cell and adjacent normal ovarian tissues. KIF20A protein expression was highly correlated with International Federation of Gynecology and Obstetrics stage (P=0.008), lymph node metastasis (P=0.002), intraperitoneal metastasis (P<0.001), vital status at last follow-up (P<0.001), intraperitoneal recurrence (P=0.030), tumor recurrence (P=0.005), drug resistance (P=0.013), and ascites with tumor cells (P<0.001). KIF20A overexpression was closely related to poorer overall survival and disease progression-free survival. Furthermore, Cox regression analysis revealed that KIF20A can act as an independent hazard indicator for predicting clinical outcomes in EOC patients. Interestingly, KIF20A overexpression promoted invasion and metastasis of EOC cells and also confers resistance to cisplatin.Conclusion: Our findings indicated that KIF20A overexpression predicts unfavorable clinical outcome, revealing that KIF20A holds a promising potential to serve as a useful prognostic biomarker for EOC patients. Keywords: epithelial ovarian cancer, KIF20A, clinical prognosis, tumor progressio