NEK2 serves as a prognostic biomarker for hepatocellular carcinoma.
NEK2 serves as a prognostic biomarker for hepatocellular carcinoma.
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DOI：
10.3892/ijo.2017.3837
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发表时间：
2017-02
影响因子：
5.2
通讯作者：
He M
中科院分区：
文献类型：
--
作者：
Li G;Zhong Y;Shen Q;Zhou Y;Deng X;Li C;Chen J;Zhou Y;He M
有丝分裂基因A（NIMA）相关激酶2（NEK 2）是一种微管相关蛋白，调节人类细胞中的纺锤体组装，并在各种恶性肿瘤中过表达。然而，NEK 2在肝细胞癌（HCC）中的作用仍不确定。我们使用Ion Proton System对HCC细胞系SMMC-7721和正常肝细胞系HL-7702进行了RNA-seq。采用定量逆转录聚合酶链反应检测NEK 2在两种细胞系和5例匹配的HCC及癌旁非肿瘤肝组织中的表达。使用可从癌症基因组图谱（TCGA）网站（https：//tcga-data.nci.nih.gov/tcga/）获得的RNASeqV 2数据，在359名患有HCC的患者中分析存活与NEK 2表达之间的相关性。采用免疫组化法检测63例HCC及相应癌旁肝组织中NEK 2、磷酸化AKT和MMP-2的表达。评估蛋白表达与临床病理参数之间的关系，并评估NEK 2与磷酸化AKT和MMP-2表达之间的相关性。转录组比较共发现610个差异表达基因（DEG），其中297个在HCC中上调，313个下调。NEK 2作为RNA-seq数据中细胞和组织中最明显不同的DEG，被列为HCC候选生物标志物以供进一步验证。NEK 2在肝癌细胞和组织中均过表达（P=0.002，P=0.013），高表达者预后差（P=0.0145）。临床分析表明，NEK 2在HCC中的过表达与肿瘤的完全性（P<0.001）、肿瘤结节数（P=0.012）和复发（P=0.004）显著相关。NEK 2与磷酸化AKT（r=0.883，P<0.01）和MMP-2（r=0.781，P<0.01）的表达呈正相关。NEK 2的过表达与临床病理特征和不良患者结局相关，表明NEK 2可作为HCC的预后生物标志物。NEK 2蛋白水平的改变可能通过激活AKT信号通路和促进MMP-2的表达而促进HCC的侵袭和转移。
Never in mitosis gene A (NIMA)-related kinase 2 (NEK2) is a microtubule-associated protein that regulates spindle assembly in human cells and is overexpressed in various malignancies. However, the role of NEK2 in hepatocellular carcinoma (HCC) remains undetermined. We performed RNA-seq of the HCC cell line SMMC-7721 and the normal liver cell line HL-7702 using the Ion Proton System. NEK2 expression was detected using quantitative reverse transcription polymerase chain reaction in two cell lines and 5 matched HCC and adjacent non-tumorous liver tissues. The correlation between survival and NEK2 expression was analyzed in 359 patients with HCC using RNASeqV2 data available from The Cancer Genome Atlas (TCGA) website (https://tcga-data.nci.nih.gov/tcga/). The expression of NEK2, phospho-AKT and MMP-2 was evaluated by immunohistochemistry in 63 cases of HCC and matched adjacent non-tumorous liver tissues. Relationships between protein expression and clinicopathological parameters were assessed, and the correlations between NEK2 with phospho-AKT and MMP-2 expressions were evaluated. A total of 610 differentially expressed genes (DEGs) were revealed in the transcriptome comparison, 297 of which were upregulated and 313 were downregulated in HCC. NEK2, as the most obviously different DEG in cells and tissues from the RNA-seq data, was listed as an HCC candidate biomarker for further verification. NEK2 was overexpressed in HCC cells and tissues (P=0.002, P=0.013) and HCC patients with a high expression of NEK2 had a poor prognosis (P=0.0145). Clinical analysis indicated that the overexpression of NEK2 in HCC was significantly correlated with diolame complete (P<0.001), tumor nodule number (P=0.012) and recurrence (P=0.004). NEK2 expression was positively correlated with the expression of phospho-AKT (r=0.883, P<0.01) and MMP-2 (r=0.781, P<0.01). Overexpression of NEK2 was associated with clinicopathological characteristics and poor patient outcomes, suggesting that NEK2 serves as a prognostic biomarker for HCC. Alteration of NEK2 protein levels may contribute to invasion and metastasis of HCC, which may occur through activation of AKT signaling and promotion of MMP-2 expression.