NIMA-Related Kinase 2 Overexpression is Associated with Poor Survival in Cancer Patients: A Systematic Review and Meta-Analysis

Abstract

NIMA-related kinase 2 (NEK2) has been reported to be overexpressed in various types of cancer and correlated with poor prognosis. The role(s) of NEK2 in cancer, however, is still uncertain. The aim of this study was to evaluate the prognostic value of NEK2 in human tumors. Methods: A comprehensive literature search was performed for PubMed, Embase, Web of Science, and CNKI databases, and eligible studies were included based on the inclusion and exclusion criteria. A meta-analysis of the included studies was then carried out. Results: Fifteen studies with 3,280 cancer patients were included in the present meta-analysis. All publications were of moderate to high quality, and had no significant heterogeneity (I 2=46% , P=0.03) or publication bias was discovered. The results showed that a high NEK2 level was associated with shorter overall survival (OS) in patients with various types of cancers (pooled HR=1.72, 95% CI 1.49-2.00, P<0.00001). However, the disease-free survival (DFS) had no significant association with NEK2 level (HR=1.13, 95% CI: 0.29-4.38, P=0.85). In the subgroup analyses, high NEK2 level was correlated with an increased risk of poor OS in patients with hepatocellular carcinoma (HR=1.62, 95% CI: 1.25-2.10, P=0.02) and lung cancer (HR=2.18, 95% CI: 1.40-3.38, P=0.0005). However, other factors, including sample size, follow-up period, HR estimation method, and country, also affect the association between NEK2 expression and OS. Analysis of clinicopathological parameters further showed that increased NEK2 level was correlated with younger age, male gender, better tumor differentiation, and lower number of tumor nodules. Conclusion: The results of this study indicated that increased expression of NEK2 was associated with unfavorable survival of cancer patients and that NEK2 could be used as a prognostic predictor for cancers.

Role of NIMA‐related kinase 2 in lung cancer: Mechanisms and therapeutic prospects

“…Kaplan-Meir analysis revealed that high expression of NEK2 in patients showed significantly poorer overall survival than those with low NEK2 expression. Thus, overexpression of NEK2 was also used as a biomarker for lung cancer [56]. Overexpression of NEK2 in different types of cancer is associated with a poor prognosis [57].…”

Never in Mitosis Kinase 2 regulation of metabolism is required for neural differentiation

“…Nek2, serving as a Gli1/2 target gene [22], also phosphorylates and stabilizes SUFU [23], placing it as negative regulator of the Hh pathway. Overexpression of Nek2 has also been linked to multiple Wnt- and Hh-associated cancers, including those causing brain malignancies [27–32].…”