Quan Chuntao, Xiao Juanjuan, Duan Qiuhong, Yuan Ping, Xue Peipei, Lu Hui, Yan Meng, Guo Dongsheng, Xu Sanpeng, Zhang Xiaohui, Lin Xuan, Wang Yong, Dogan Soner, Zhang Jianmin, Zhu Feng, Ke Changshu, Liu Lin
Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
Department of Pathology, Affiliated Tianyou Hospital of Wuhan University of Science and Technology, Wuhan, Hubei, PR China.
Oncotarget. 2017 Dec 26;9(8):7782-7795. doi: 10.18632/oncotarget.23674. eCollection 2018 Jan 30.
TOPK is overexpressed in various types of cancer and associated with poor outcomes in different types of cancer. In this study, we first found that the expression of T-lymphokine-activated killer cell-originated protein kinase (TOPK) was significantly higher in Grade III or Grade IV than that in Grade II in glioma ( = 0.007 and < 0.001, respectively). Expression of TOPK was positively correlated with Ki67 ( < 0.001). Knockdown of TOPK significantly inhibited cell growth, colony formation and increased sensitivities to temozolomide (TMZ) in U-87 MG or U-251 cells, while TOPK overexpression promoted cell growth and colony formation in Hs 683 or A-172 cells. Glioma patients expressing high levels of TOPK have poor survival compared with those expressing low levels of TOPK in high-grade or low-grade gliomas (hazard ratio = 0.2995; 95% CI, 0.1262 to 0.7108; = 0.0063 and hazard ratio = 0.1509; 95% CI, 0.05928 to 0.3842; < 0.0001, respectively). The level of TOPK was low in TMZ-sensitive patients compared with TMZ-resistant patients ( = 0.0056). In TMZ-resistant population, patients expressing high TOPK have two months' shorter survival time than those expressing low TOPK. Our findings demonstrated that TOPK might represent as a promising prognostic and predictive factor and potential therapeutic target for glioma.
TOPK在多种类型的癌症中过表达，并与不同类型癌症的不良预后相关。在本研究中，我们首先发现，在胶质瘤中，III级或IV级的T淋巴细胞激活的杀伤细胞源蛋白激酶（TOPK）表达显著高于II级（分别为 = 0.007和 < 0.001）。TOPK的表达与Ki67呈正相关（< 0.001）。敲低TOPK可显著抑制U - 87 MG或U - 251细胞的生长、集落形成，并增加对替莫唑胺（TMZ）的敏感性，而TOPK过表达则促进Hs 683或A - 172细胞的生长和集落形成。与高等级或低等级胶质瘤中低水平表达TOPK的患者相比，高水平表达TOPK的胶质瘤患者生存率较差（风险比 = 0.2995；95%可信区间，0.1262至0.7108； = 0.0063和风险比 = 0.1509；95%可信区间，0.05928至0.3842；< 0.0001）。与TMZ耐药患者相比，TMZ敏感患者的TOPK水平较低（ = 0.0056）。在TMZ耐药人群中，高表达TOPK的患者比低表达TOPK的患者生存时间短两个月。我们的研究结果表明，TOPK可能是一种有前景的胶质瘤预后和预测因子以及潜在的治疗靶点。
