Li Han, Zhang Weijing, Sun Xiaoying, Chen Jueming, Li Yue, Niu Chunhao, Xu Benke, Zhang Yanna
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China,
Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, Guangdong, China,
Cancer Manag Res. 2018 Sep 12;10:3433-3450. doi: 10.2147/CMAR.S169214. eCollection 2018.
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.
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.
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 (=0.008), lymph node metastasis (=0.002), intraperitoneal metastasis (<0.001), vital status at last follow-up (<0.001), intraperitoneal recurrence (=0.030), tumor recurrence (=0.005), drug resistance (=0.013), and ascites with tumor cells (<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.
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.
KIF20A在胞质分裂调控中发挥不可或缺的作用，这对肿瘤增殖和生长至关重要。最近，KIF20A的致癌作用在几种癌症中已有充分记载。然而，其在上皮性卵巢癌（EOC）中的临床作用尚未见报道。我们研究了其在EOC细胞中的表达及其在促进侵袭和化疗耐药中的作用。
通过实时定量聚合酶链反应和蛋白质印迹法，研究正常卵巢上皮细胞、卵巢癌细胞以及10对新鲜EOC组织和相邻正常卵巢组织中KIF20A的转录和翻译水平。此外，还通过免疫组织化学法检测了150例EOC组织中的KIF20A蛋白水平。采用统计学方法分析KIF20A表达与临床变量之间的相关性。我们还使用伤口愈合试验、Transwell试验、MTT法和Annexin V/PI法来探究KIF20A的功能。
与正常卵巢上皮细胞和相邻正常卵巢组织相比，EOC细胞系和临床癌组织中KIF20A的mRNA和蛋白水平均明显升高。KIF20A蛋白表达与国际妇产科联盟分期（=0.008）、淋巴结转移（=0.002）、腹腔转移（<0.001）、最后随访时的生命状态（<0.001）、腹腔复发（=0.030）、肿瘤复发（=0.005）、耐药（=0.013）以及腹水伴肿瘤细胞（<0.001）高度相关。KIF20A过表达与较差的总生存期和无疾病进展生存期密切相关。此外，Cox回归分析显示，KIF20A可作为预测EOC患者临床结局的独立危险因素。有趣的是，KIF20A过表达促进了EOC细胞的侵袭和转移，并且还赋予了对顺铂的耐药性。
我们的研究结果表明，KIF20A过表达预示着不良的临床结局，这表明KIF20A有潜力成为EOC患者有用的预后生物标志物。
