Ma Zebiao, Wang Xiaojing, He Jiehua, Xia Jianchuan, Li Yanfang
Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong, P. R. China.
Department of Gynecologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P. R. China.
PLoS One. 2017 Mar 29;12(3):e0174037. doi: 10.1371/journal.pone.0174037. eCollection 2017.
Epithelial ovarian cancer (EOC) is one of the deadly gynecological malignancies. The function of protein kinase CK2α (CK2α) in EOC is still unknown. Our study aimed to investigate the relationship between the protein expression of CK2α and the tumor progression, the prognosis of human EOC. In this study, we analyzed the expression levels of CK2α through Western blot, using EOC cell lines like A2780, HO8910, COV644, OVCAR3, SKOV3, and the primary normal ovarian surface epithelial (NOSE) cells. Furthermore, OVCAR3 and SKOV3 EOC cells were employed as a cellular model to study the role of CK2α on cell growth, migration, invasion, apoptosis, and cell cycle distribution. In addition, we investigated CK2α protein expression in tumor tissues from patients with EOC by immunohistochemistry and analyzed the association between CK2α expression and clinicopathologic parameters and prognosis of EOC patients. And we found that compared with NOSE cells, CK2α protein expression was increased in A2780, HO8910, OVCAR3, and SKOV3 ovarian cancer cell lines. Decreased CK2α expression suppressed OVCAR3 and SKOV3 cell growth and induced more apoptosis. CK2α knockdown using specific siRNAs inhibited migration and invasion ability of OVCAR3 and SKOV3 cells. In addition, high CK2α protein expression was found in 68.4% (80/117) of EOC patients. Increased CK2α expression of was significantly correlated with FIGO staging and peritoneal cytology. Patients with higher CK2α expression had a significantly poorer overall survival compared with those with lower CK2α expression. Multi-variate Cox regression analysis proved that increased CK2α expression was an independent prognostic marker for EOC. Taken together, our data displayed that CK2α may play a role in tumor aggressive behavior of EOC and could be used as a marker for predicting prognosis of EOC patient. High CK2α expression might predict poor patient survival.
上皮性卵巢癌(EOC)是致命的妇科恶性肿瘤之一。蛋白激酶CK2α(CK2α)在EOC中的功能尚不清楚。我们的研究旨在探讨CK2α蛋白表达与人类EOC肿瘤进展及预后之间的关系。在本研究中,我们通过蛋白质印迹法分析了CK2α在A2780、HO8910、COV644、OVCAR3、SKOV3等EOC细胞系以及原代正常卵巢表面上皮(NOSE)细胞中的表达水平。此外,采用OVCAR3和SKOV3 EOC细胞作为细胞模型,研究CK2α对细胞生长、迁移、侵袭、凋亡及细胞周期分布的作用。另外,我们通过免疫组织化学研究了EOC患者肿瘤组织中CK2α蛋白的表达,并分析了CK2α表达与EOC患者临床病理参数及预后的相关性。我们发现,与NOSE细胞相比,A2780、HO8910、OVCAR3和SKOV3卵巢癌细胞系中CK2α蛋白表达增加。CK2α表达降低抑制了OVCAR3和SKOV3细胞的生长并诱导了更多的细胞凋亡。使用特异性小干扰RNA敲低CK2α可抑制OVCAR3和SKOV3细胞的迁移和侵袭能力。此外,在68.4%(80/117)的EOC患者中发现CK2α蛋白高表达。CK2α表达增加与国际妇产科联盟(FIGO)分期及腹腔细胞学显著相关。与CK2α表达较低的患者相比,CK2α表达较高的患者总生存期明显较差。多因素Cox回归分析证明,CK2α表达增加是EOC的独立预后标志物。综上所述,我们的数据表明CK2α可能在EOC的肿瘤侵袭行为中起作用,并可作为预测EOC患者预后的标志物。CK2α高表达可能预示患者生存不良。