High KIF2A expression predicts unfavorable prognosis in diffuse large B cell lymphoma

Yaping Zhang,Li Yang,Hong Liu,Mengqi Xu,Xuefen You,Qingxiu Dang,Wenyu Shi,Jianfei Huang

doi:10.1007/s00277-017-3047-1

Abstract

Kinesin family member 2A (KIF2A), a conserved motor protein, plays a critical role in the pathogenesis and prognosis of several malignant tumors. The aim of the present study was to investigate KIF2A expression in diffuse large B cell lymphoma (DLBCL), evaluate the association between KIF2A expression and the clinical parameters of the disease, and determine its prognostic value. KIF2A expression was evaluated in 134 DLBCL and 57 reactive hyperplasia samples using immunohistochemistry on a tissue microarray. The correlations between KIF2A expression with clinical parameters and prognosis were estimated using univariate and multivariate analyses. The expression of KIF2A was significantly higher in DLBCL tissue samples compared with those from subjects with reactive hyperplasia (P=0.002). Furthermore, increased expression of KIF2A protein in DLBCL was related to Ann Arbor stage (P=0.027) and international prognostic index (IPI) score (P=0.01). The survival analysis showed that KIF2A expression (P=0.016), serum LDH level (P=0.049), and IPI score (P<0.001) were independent prognostic markers for DLBCL. Our findings also confirmed that downregulating KIF2A expression decreased tumor cell viability, accompanied by downregulation of pAKT levels. Taken together, these data provide the first evidence that increased KIF2A expression predicts poor prognosis in patients with DLBCL, and a rationale for treatment of DLBCL by targeting KIF2A.

Highlights

Diffuse large B cell lymphoma (DLBCL), the aggressive subtype of malignant lymphomas, accounts for 30–40% of all lymphomas
Prior studies demonstrated that overexpression of kinesin family member 2A (KIF2A) may be involved in the carcinogenesis of breast cancer [10], squamous cell carcinoma of the oral tongue (SCCOT) [11], colorectal cancer [12], and ovarian cancer [13]
Our study aimed to explore the expression of KIF2A in DLBCL, its correlation with clinical parameters, and the prognostic role of KIF2A expression in DLBCL

Summary

Introduction

Diffuse large B cell lymphoma (DLBCL), the aggressive subtype of malignant lymphomas, accounts for 30–40% of all lymphomas. Treatment remains suboptimal in roughly 30% of DLBCL patients [2]. The kinesin-13 family, which includes kinesin family member 2A (KIF2A), KIF2B, and KIF2C/MCAK, is microtubule depolymerases that play a critical role in mitotic activity [3, 4]. These proteins regulate cytokinesis, mitotic spindle formation, and cell division [5, 6]. Specific siRNA- or antibody-mediated knockdown of KIF2A expression results in the formation of monopolar spindles and arrest of cell cycle progression [8, 9]. We show that the expression of KIF2A protein was elevated in DLBCL patients and was correlated with adverse

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