Department of Dermatology, Linyi Central Hospital, Linyi, Shandong, China.
Eur Rev Med Pharmacol Sci. 2018 Jun;22(12):3694-3702. doi: 10.26355/eurrev_201806_15248.
Never in Mitosis (NIMA) Related Kinase 2 (Nek2) is a serine/threonine-protein kinase encoded by the NEK2 gene and is an essential enzyme in cell cycle progression. In this study, we investigated NEK2 expression profile, its independent prognostic value in terms of recurrence-free survival (RFS)/overall survival (OS), and the potential mechanisms of its dysregulation in melanoma.
A retrospective study was conducted using data from Gene Expression Omnibus (GEO) datasets and the Cancer Genome Atlas (TCGA)-skin cutaneous melanoma (SKCM).
NEK2 was significantly upregulated in melanoma tissues. NEK2 upregulation independently predicted poor OS (HR: 1.500, 95% CI: 1.092-2.059, p = 0.012) and RFS (HR: 2.213, 95% CI: 1.298-3.772, p = 0.004). NEK2 DNA amplification was common in melanoma (192/366, 52.5%), which was associated with significantly elevated NEK2 expression. NEK2 expression was weakly and negatively correlated with its DNA methylation (Pearson's r = -0.29). Loss of p53 was associated with increased NEK2 expression.
Based on findings above, we infer that NEK2 expression independently predicts poor survival of melanoma. Its dysregulation might be related to DNA amplification/methylation and TP53 mutation.
有丝分裂期检查点激酶 2（NIMA 相关激酶 2，Nek2）是丝氨酸/苏氨酸蛋白激酶，由 NEK2 基因编码，是细胞周期进程中的必需酶。在本研究中，我们研究了 NEK2 的表达谱，以及其在无复发生存率（RFS）/总生存率（OS）方面的独立预后价值，并探讨了其在黑色素瘤中失调的潜在机制。
使用来自基因表达综合数据库（GEO）数据集和癌症基因组图谱（TCGA）-皮肤黑色素瘤（SKCM）的数据进行回顾性研究。
NEK2 在黑色素瘤组织中显著上调。NEK2 上调独立预测总生存期（HR：1.500，95%CI：1.092-2.059，p=0.012）和 RFS（HR：2.213，95%CI：1.298-3.772，p=0.004）不良。黑色素瘤中常见 NEK2 基因扩增（192/366，52.5%），与 NEK2 表达显著升高相关。NEK2 表达与 DNA 甲基化呈弱负相关（Pearson's r=-0.29）。p53 缺失与 NEK2 表达增加相关。
基于上述发现，我们推断 NEK2 表达独立预测黑色素瘤患者的不良预后。其失调可能与 DNA 扩增/甲基化和 TP53 突变有关。
