T-lymphokine-activated killer cell-originated protein kinase (TOPK) as a prognostic factor and a potential therapeutic target in glioma

• Published in: Oncotarget 2018-01, Vol.9 (8), p.7782-7795
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Research Paper
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.23674

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.