title: NEK2 serves as a prognostic biomarker for hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Department of Pharmacy, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.
authors.forename: Qingrong
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: School of Public Health, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Deng
authors.affiliation: School of Public Health, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Li
authors.affiliation: School of Public Health, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Jiagui
authors.initials: J
authors.lastname: Chen
authors.affiliation: School of Public Health, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: School of Public Health, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: He
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D000072379:NIMA-Related Kinases / Q000032:analysis / Q000096:biosynthesis*; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; C089441:NEK2 protein, human; D000072379:NIMA-Related Kinases