Clinical Significance of Sphingosine Kinase-1 Expression in Human Astrocytomas Progression and Overall Patient Survival
Clinical Significance of Sphingosine Kinase-1 Expression in Human Astrocytomas Progression and Overall Patient Survival
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DOI：
10.1158/1078-0432.ccr-08-0754
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发表时间：
2008-11-01
影响因子：
11.5
通讯作者：
Li, Mengfeng
中科院分区：
文献类型：
--
作者：
Li, Jun;Guan, Hong-Yu;Li, Mengfeng
目的：为探讨神经鞘氨醇激酶1（SPHK 1）在人脑星形细胞瘤中的表达及其与星形细胞瘤发生、发展的关系，采用定量逆转录聚合酶链反应（RT-PCR）和免疫印迹法检测SPHK 1在正常人脑星形胶质细胞、星形细胞瘤细胞系、4对星形细胞瘤组织及其癌旁正常脑组织中的表达。此外，SPHK 1蛋白表达检测243例星形细胞瘤的组织学特征的免疫组化。统计分析应用于测试预后和诊断association.Results：SPHK 1在星形细胞瘤细胞系的mRNA和蛋白质水平均升高，SPHK 1的mRNA和蛋白质分别显著上调高达6.8和40倍，分别在原发性星形细胞瘤与那些在邻近的非癌脑组织。免疫组化分析显示，100（41.2%）243石蜡包埋存档星形细胞瘤活检SPHK 1高表达。SPHK 1表达水平与星形细胞瘤的组织学分级密切相关（P = 0.000），SPHK 1表达水平高的星形细胞瘤患者生存期短（P < 0.001）。多变量分析显示SPHK 1上调可能是星形细胞瘤患者生存的独立预后指标。结论：SPHK 1可能是星形细胞瘤一种新的有用的预后标志物，并在疾病的发生和进展中发挥作用。
Purpose: To characterize the expression of sphingosine kinase-1 (SPHK1) in human astrocytomas and to investigate the association between SPHK1 expression and progression of astrocytomas.Experimental Design: The expression of SPHK1 in normal human astrocytes, astrocytoma cell lines, and four pairs of matched astrocytoma tissues and their adjacent normal brain tissues were detected by quantitative reverse transcription-PCR and Western blot. In addition, SPHK1 protein expression was examined in 243 cases of histologically characterized astrocytomas by immunohistochemistry. Statistical analyses were applied to test for prognostic and diagnostic associations.Results: SPHK1 in astrocytoma cell lines was elevated at both mRNA and protein levels, and the SPHK1 mRNA and protein were significantly up-regulated by up to 6.8- and 40-fold, respectively, in primary astrocytomas compared with those in the adjacent noncancerous brain tissues. Immunohistochemical analysis showed that 100 of 243 (41.2%) paraffin-embedded archival astrocytoma biopsies exhibited high expression of SPHK1. Statistical analysis suggested that the up-regulation of SPHK1 was significantly correlated with the histologic grade of astrocytoma (P = 0.000) and that patients with high SPHK1 level exhibited shorter survival time (P < 0.001). Multivariate analysis revealed that SPHK1 up-regulation might be an independent prognostic indicator for the survival of patients with astrocytoma.Conclusions: SPHK1 might represent a novel and useful prognostic marker for astrocytoma and play a role during the development and progression of the disease.