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一种新型电压门控钾通道——Kv 1.5在星形细胞瘤中的差异表达及其对胶质母细胞瘤预后的影响。

Differential expression of a novel voltage gated potassium channel--Kv 1.5 in astrocytomas and its impact on prognosis in glioblastoma.

作者信息

Arvind S, Arivazhagan A, Santosh V, Chandramouli B A

机构信息

Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, India.

出版信息

Br J Neurosurg. 2012 Feb;26(1):16-20. doi: 10.3109/02688697.2011.583365. Epub 2011 Jun 27.

DOI:10.3109/02688697.2011.583365
PMID:21707241
Abstract

INTRODUCTION

Ion channels are subjects of intense research, due to their easy access and potential for being drug targets. Kv1.5 is a voltage gated potassium channel, earlier thought to be cardiac specific. Recent studies have revealed that K(+) channels play an important role in apoptosis, glial cell proliferation and biology of various cancers. No study has so far been performed to assess their expression in astrocytomas and correlate its impact on the clinical behaviour of gliomas.

METHODS

Sixty samples of astrocytoma which included 9 diffuse astrocytoma (DA) grade II, 11 anaplastic astrocytoma (AA) grade III and 40 glioblastoma (GBM), along with normal brain tissue (cerebral cortex; n = 5) were analysed for their Kv1.5 protein expression. Immunohistochemical expression of Kv1.5 in various grades was assessed semi quantitatively. The patients with GBM (n = 40) were treated with uniform protocol and their survival was documented.

RESULTS

The mean expression of Kv1.5 in DA, AA and GBM was 22.2 ± 9.71%, 11.81 ± 12.3% and 10.37 ± 11.05%, respectively, the difference being statistically significant (p = 0.004). The mean expression in low grade astrocytoma (WHO II) was significantly higher than higher grades (22.2% and 10.7%; p = 0.005). On analysing the influence of Kv1.5 expression on survival of GBM patients, we noted that increasing Kv1.5 labelling index (LI) correlated with a favourable prognosis, albeit not being significant (p = 0.310; HR = 0.901).

CONCLUSIONS

Kv1.5 expression occurs more in DA, when compared to high grade astrocytoma. GBM patients with higher Kv1.5 expression had better survival, though not reaching statistical significance.

摘要

引言

离子通道因其易于研究且具有作为药物靶点的潜力,成为了深入研究的对象。Kv1.5是一种电压门控钾通道,早期被认为具有心脏特异性。最近的研究表明,钾离子通道在细胞凋亡、胶质细胞增殖以及各种癌症生物学过程中发挥着重要作用。目前尚未有研究评估其在星形细胞瘤中的表达情况,以及其对胶质瘤临床行为的影响。

方法

分析了60份星形细胞瘤样本,其中包括9例二级弥漫性星形细胞瘤(DA)、11例三级间变性星形细胞瘤(AA)和40例胶质母细胞瘤(GBM),同时分析了正常脑组织(大脑皮层;n = 5)的Kv1.5蛋白表达。对不同级别中Kv1.5的免疫组化表达进行半定量评估。对40例GBM患者采用统一方案进行治疗,并记录其生存情况。

结果

DA、AA和GBM中Kv1.5的平均表达分别为22.2 ± 9.71%、11.81 ± 12.3%和10.37 ± 11.05%,差异具有统计学意义(p = 0.004)。低级别星形细胞瘤(世界卫生组织二级)中的平均表达显著高于高级别(22.2%和10.7%;p = 0.005)。在分析Kv1.5表达对GBM患者生存的影响时,我们注意到Kv1.5标记指数(LI)的增加与良好预后相关,尽管不显著(p = 0.310;HR = 0.901)。

结论

与高级别星形细胞瘤相比,DA中Kv1.5表达更多。Kv1.5表达较高的GBM患者生存情况较好,尽管未达到统计学意义。

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