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

Chuntao Quan,Juanjuan Xiao,Xiaohui Zhang,Peipei Xue,Ping Yuan,Soner Dogan,Jianmin Zhang,Yong Wang,Qiuhong Duan,Meng Yan,Changshu Ke,Feng Zhu,Hui Lu,Xuan Lin,Sanpeng Xu,Lin Liu,Dongsheng Guo

doi:10.18632/oncotarget.23674

Abstract

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.

Highlights

Glioma represents the most common primary tumor in the Central Nervous System (CNS)
We examine the expression of Ki67, P53 and EGFR, common molecules associated with histological grade or prognosis in human glioma
We found that P53 and EGFR were expressed in low-grade gliomas (LGG) or high-grade gliomas (HGG), and no significant difference between Grade II and Grade III or Grade IV (P > 0.05) (Figure 1C and 1D)

Summary

Introduction

Glioma represents the most common primary tumor in the Central Nervous System (CNS). Malignant glioma often leads to fatal outcomes because of its biological behavior and its resistance to current therapies, posing great challenges to public health. The classification of glioma has been mostly based on histopathological features. Some patients with histologically identical tumors have very different outcomes and responses to treatment. Integration of both histological and molecular biomarkers was introduced in the 2016 World Health Organization (WHO) Classification of CNS tumors [2]. It is critical to identify important candidates to improve our understanding on the pathogenesis, diagnosis, clinical therapeutic decision and prognosis evaluation in malignant glioma patients

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Results

Conclusion