The Prognostic Significance of NEK2 in Hepatocellular Carcinoma: Evidence from a Meta-Analysis and Retrospective Cohort Study

Abstract

Background/Aims: Numerous studies have shown that NIMA-related kinase 2 (NEK2) expression in hepatocellular carcinoma (HCC) tissue is associated with survival and clinicopathological features; however, the evidence remains inconclusive. Thus, we aimed to further explore the prognostic and clinicopathological significance of NEK2 expression in HCC using a two-part study consisting of a retrospective cohort study and a meta-analysis. Methods: In the cohort study, NEK2 expression in 206 HCC samples and adjacent normal liver tissues was detected by immunohistochemistry (IHC). Patients were divided into a high NEK2 expression group and a low NEK2 expression group by the median value of the immunohistochemical scores. The Kaplan–Meier method with the log-rank test was used to analyze survival outcomes in the two groups, and multivariate analysis based on Cox proportional hazard regression models was applied to identify independent prognostic factors. In the meta-analysis, eligible studies were searched in PubMed, EMBASE, Web of Science, and CNKI databases. STATA version 12.0 (Stata Corporation, College Station, TX) was used for statistical analyses. Results: The IHC results of our cohort study showed higher NEK2 expression in HCC tissues compared with adjacent normal liver tissues. Multivariate analysis revealed that high NEK2 expression was an independent risk factor for poor overall survival (OS) [hazard ratio (HR) = 1.763; 95% CI, 1.060–2.935; P = 0.029] and disease-free survival (DFS) [hazard ratio (HR) = 1.687; 95% CI, 1.102–2.584; P = 0.016] in HCC patients. A total of 11 studies with 1,698 patients were enrolled in the meta-analysis, consisting of 10 studies from the database search and our cohort study. The pooled results revealed that high NEK2 expression correlated closely with poor OS among HCC patients (HR = 1.47; 95% CI, 1.21–1.80; P < 0.01), and DFS/recurrence-free survival (RFS) (HR = 1.92; 95% CI, 1.41–2.63; P < 0.01). Additionally, our meta-analysis also showed that the proportion of HCC patients with high NEK2 expression was greater in the group with larger tumors (> 5 cm) than in the group with smaller tumors (≤ 5 cm) [odds ratio (OR) = 2.02; 95% CI, 1.13–3.64; P < 0.01). Conclusion: Our study demonstrated that high NEK2 expression is a risk factor for poor survival in HCC patients. More prospective, homogeneous, and multiethnic studies are required to validate our findings.

Identification of Key Genes Associated With the Process of Hepatitis B Inflammation and Cancer Transformation by Integrated Bioinformatics Analysis

“…This is very similar to our results ( Xie et al, 2019 ). Cheng et al (2018) found in a cohort study that a high expression of NEK2 was an independent risk factor for decreased OS. The results of the study suggest that a high expression of NEK2 is a risk factor for poor survival of liver cancer patients ( Cheng et al, 2018 ; Ren et al, 2018 ).…”

Identification and Validation of a Reliable Prognostic Eleven-Genes Signature for Hepatocellular Carcinoma

“…Elevation of NEK2 will contribute to premature centrosome splitting, concomitant with centrosomal abnormalities, monopolar spindles and aneuploidy [29]. Previous studies have reported that it was overexpressed in numerous cancer cell lines and associated closely with tumor size, portal vein invasion and poor tumor differentiation [30]. Zhang et al reported that over-expression of NEK2 could promote the proliferation of HepG2 cells by activating the mitogen-activated protein kinase (MAPK) signaling pathway [31] and interfering or silencing NEK2 expression can suppress HepG2 cells' cell growth and invasion, promote apoptosis and cycle arrest [32].…”

ADAM17-regulated CX3CL1 expression produced by bone marrow endothelial cells promotes spinal metastasis from hepatocellular carcinoma

“…prognosis of patients with HCC (43,44). Both the PTK2 inhibitor, PF562271, and the PIK3CA inhibitor, LY294002, downregulated the CX3CL1-induced activation of p-AKT1 (Tyr308/Ser473) (Fig.…”