T-lymphokine-activated killer cell-originated protein kinase (TOPK) as a prognostic factor and a potential therapeutic target in glioma
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Chuntao Quan1,*, Juanjuan Xiao1,*, Qiuhong Duan1, Ping Yuan1, Peipei Xue1, Hui Lu1, Meng Yan2, Dongsheng Guo3, Sanpeng Xu4, Xiaohui Zhang5, Xuan Lin6, Yong Wang7, Soner Dogan8, Jianmin Zhang1, Feng Zhu1, Changshu Ke4 and Lin Liu1
1Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei, PR China
2Department of Pathology, Affiliated Tianyou Hospital of Wuhan University of Science and Technology, Wuhan, Hubei, PR China
3Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China
4Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China
5Department of Hematopathology and Laboratory Medicine, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
6Department of Endocrinology, China Resources and WISCO General Hospital, Wuhan, Hubei, PR China
7School of Medicine, Yichun University, Yuanzhou District, Yichun, Jiangxi, PR China
8School of Medicine, Yeditepe University, Istanbul, Turkey
*These authors contributed equally to this work
Feng Zhu, email: email@example.com
Changshu Ke, email: firstname.lastname@example.org
Lin Liu, email: email@example.com
Keywords: glioma; TOPK; prognostic factor; TMZ; drug resistance
Received: July 10, 2017 Accepted: December 11, 2017 Published: December 26, 2017
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 (P = 0.007 and P < 0.001, respectively). Expression of TOPK was positively correlated with Ki67 (P < 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; P = 0.0063 and hazard ratio = 0.1509; 95% CI, 0.05928 to 0.3842; P < 0.0001, respectively). The level of TOPK was low in TMZ-sensitive patients compared with TMZ-resistant patients (P = 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.
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