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驱动蛋白家族成员 14 是预测脑胶质瘤患者预后的候选标志物。

Kinesin family member 14 is a candidate prognostic marker for outcome of glioma patients.

机构信息

Department of Experimental Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an City 710032, China.

出版信息

Cancer Epidemiol. 2013 Feb;37(1):79-84. doi: 10.1016/j.canep.2012.08.011. Epub 2012 Sep 21.

DOI:10.1016/j.canep.2012.08.011
PMID:22999822
Abstract

BACKGROUND & AIM: Human kinesin superfamily proteins (KIFs) are a conserved class of microtubule-dependent molecular motor proteins with adenosine triphosphatase activity and motion characteristics. As a member of KIFs, KIF14 plays an important role in the regulation of cell cycle and mitotic progression. Deregulation of KIF14 has been found in several human malignancies and also has been demonstrated to be involved in tumor progression and related to patient survival. The aim of this study was to investigate the clinicopathological significance of KIF14 expression in glioma.

METHODS

Real-time quantitative RT-PCR assay was performed to detect KIF14 mRNA expression, and Western blot and immunohistochemistry analyses were performed to detect KIF14 protein expression in human gliomas and non-neoplastic brain tissues, respectively. Then, the association of KIF14 immunostaining with clinicopathological factors and prognosis of glioma patients was also statistically analyzed.

RESULTS

KIF14 mRNA and protein expression were respectively increased 5.5- and 4.2-fold on average in glioma tissues relative to non-neoplastic brain tissues (both P < 0.001). Additionally, both KIF14 mRNA and protein expression increased with ascending pathological grade. Then, the high KIF14 immunostaining in glioma tissues was significantly associated with advanced pathological grade (P = 0.008), low Karnofsky performance score (KPS) (P = 0.02), high mitotic index (P = 0.005) and Ki-67 index (P = 0.008). Furthermore, both univariate and multivariate Cox regression analyses determined that KIF14 overexpression effectively predicted decreased overall survival in patients with gliomas.

CONCLUSIONS

These findings offer the first convinced evidence that KIF14 expression in gliomas is tumor-specific and increased in more aggressive tumors. KIF14 might function as a candidate prognostic marker for human gliomas.

摘要

背景与目的

人类驱动蛋白超家族蛋白(KIFs)是一类保守的微管依赖性分子马达蛋白,具有三磷酸腺苷酶活性和运动特征。作为 KIFs 的一员,KIF14 在细胞周期调控和有丝分裂进展中发挥重要作用。KIF14 的失调已在几种人类恶性肿瘤中发现,并已证明与肿瘤进展有关,与患者的生存有关。本研究旨在探讨 KIF14 表达在神经胶质瘤中的临床病理意义。

方法

实时定量 RT-PCR 检测 KIF14mRNA 表达,Western blot 和免疫组化分析分别检测 KIF14 蛋白在人神经胶质瘤和非神经组织中的表达。然后,还统计分析了 KIF14 免疫染色与神经胶质瘤患者临床病理因素和预后的关系。

结果

KIF14mRNA 和蛋白表达在神经胶质瘤组织中分别平均增加了 5.5 倍和 4.2 倍(均 P <0.001)。此外,KIF14mRNA 和蛋白表达均随病理分级升高而升高。然后,神经胶质瘤组织中高 KIF14 免疫染色与高级别病理分级(P = 0.008)、低卡诺夫斯基表现评分(KPS)(P = 0.02)、高有丝分裂指数(P = 0.005)和 Ki-67 指数(P = 0.008)显著相关。此外,单因素和多因素 Cox 回归分析均确定 KIF14 过表达可有效预测神经胶质瘤患者总生存期缩短。

结论

这些发现首次提供了令人信服的证据,表明神经胶质瘤中 KIF14 的表达是肿瘤特异性的,并且在侵袭性更强的肿瘤中增加。KIF14 可能是人类神经胶质瘤的候选预后标志物。

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