Low expression of NEK2 is associated with hepatocellular carcinoma progression and poor prognosis

Article type: Research Article

Authors: Fu, Luoqin^{a; 1} | Liu, Suxia^{b; c; 1} | Wang, Huiju^a | Ma, Yingyu^a | Li, Li^a | He, Xianglei^d | Mou, Xiaozhou^a | Tong, Xiangmin^{a; b; c} | Hu, Zhiming^{a; e} | Ru, Guoqing^{d; *}

Affiliations: [a] Clinical Research Institute, Zhejiang Provincial People’s Hospital, Hangzhou 310014, Zhejiang, China | [b] School of Medicine, Zhejiang University, Hangzhou 310000, Zhejiang, China | [c] Department of Clinical Laboratory, Lishui Central Hospital, Lishui 323000, Zhejiang, China | [d] Department of Pathology, Zhejiang Provincial People’s Hospital, Hangzhou 310014, Zhejiang, China | [e] Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People’s Hospital, Hangzhou 310014, Zhejiang, China

Correspondence: [*] Corresponding author: Guoqing Ru, Department of Pathology, Zhejiang Provincial People’s Hospital, No. 158 Shangtang Road, Hangzhou 310014, Zhejiang, China. Tel.: +86 571 85893289; Fax: +86 571 85893833; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: BACKGROUND: NIMA-related kinase 2 (NEK2), a serine/threonine kinase, is located in the centrosome and is a member of cell cycle regulation related protein kinase (CCRK) family. Aberrant expression of NEK2 is linked with carcinogenesis and progression of various tumors. OBJECTIVE: To investigate the expression level of NEK2 and its relationship with clinicopathological factors in hepatocellular carcinoma (HCC). METHODS: Immunohistochemistry was used to measure the expression of NEK2 in 310 patients’ specimen tissues and 197 adjacent normal liver tissues of HCC cases, and the subsequent prognostic value for each sample was estimated. RESULTS: NEK2 expression levels in HCC were lower than in adjacent tissues (49.7% vs. 72.6%, P< 0.001). First, patients with relatively low NEK2 expression had increased cancer progression and poorer prognosis than those with high expression. Second, NEK2 expression was significantly reduced in patients with large tumors (P= 0.025), with stage III Edmondson-Steiner Grading (P= 0.015). Third, patients’ tumor size positively correlated with high AFP concentration (P= 0.017). Fourth, using the Kaplan-Meier survival curve, we found a lower survival rate in patients with decreased expression of NEK2 than those with high NEK2 expression in HCC (P= 0.029, Log-rank test). CONCLUSIONS: Low NEK2 expression might be a useful predictor in HCC as a poor prognostic factor, and could serve as a potential therapeutic target for HCC.

Keywords: NIMA-related kinase 2, hepatocellular carcinoma, immunohistochemistry, prognostic factors

DOI: 10.3233/CBM-170586

Journal: Cancer Biomarkers, vol. 20, no. 1, pp. 101-106, 2017