The expression level of sphingosine-1-phosphate receptor type 1 is related to MIB-1 labeling index and predicts survival of glioblastoma patients
The expression level of sphingosine-1-phosphate receptor type 1 is related to MIB-1 labeling index and predicts survival of glioblastoma patients
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DOI：
10.1007/s11060-009-0064-5
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发表时间：
2010-05
影响因子：
3.9
通讯作者：
Y. Yoshida;M. Nakada;Tomoya Harada;Shingo Tanaka;T. Furuta;Y. Hayashi;D. Kita;N. Uchiyama;Y. Hayashi;J. Hamada
中科院分区：
文献类型：
--
作者：
Y. Yoshida;M. Nakada;Tomoya Harada;Shingo Tanaka;T. Furuta;Y. Hayashi;D. Kita;N. Uchiyama;Y. Hayashi;J. Hamada
尽管有许多关于MIB-1标记指数（LI）临床应用的报告，该指数是星形细胞瘤增殖活性的衡量标准;其意义在不同研究之间存在差异。在星形细胞瘤中，没有已知的分子与MIB-1 LI直接相关。我们评估了MIB-1 LI在人类胶质母细胞瘤病例中的临床价值，并确定了可能影响MIB-1 LI的分子。MIB-1蛋白的免疫组化研究进行了38胶质母细胞瘤和MIB-1 LI测定。在相同的情况下，表皮生长因子受体（EGFR），血小板衍生生长因子受体-α（PDGFRA）和鞘氨醇-1-磷酸受体1型（S1 P1），这是已知的神经胶质瘤细胞增殖的调节剂，检测和定量的实时PCR或蛋白质印迹。Kaplan-Meier生存曲线显示MIB-1高LI与低生存率相关（P< 0.05）。在所检测的分子中，只有S1 P1的低表达与MIB-1的高LI显著相关（P< 0.05）。多因素分析显示S1 P1表达水平是影响预后的重要因素。我们的研究结果表明，MIB-1 LI是一个重要的预后因素，在人类胶质母细胞瘤。此外，S1 P1表达的下调增加了增殖活性，从而增强了胶质母细胞瘤的恶性程度，导致生存率低。
Although there are many reports on the clinical use of the MIB-1 labeling index (LI), which is a measure of proliferative activity in astrocytomas; its significance varies between studies. There are no known molecules that are directly linked to the MIB-1 LI in astrocytomas. We evaluated the clinical value of the MIB-1 LI in our human glioblastoma cases and determined the molecules that possibly influenced the MIB-1 LI. An immunohistochemical study of the MIB-1 protein was performed and MIB-1 LIs of 38 glioblastomas were determined. In the same cases, epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor-α (PDGFRA), and sphingosine-1-phosphate receptor type 1 (S1P1), which are known regulators of glioma cell proliferation, were detected and quantified by quantitative real-time-PCR or western blotting. Kaplan–Meier survival curves for 38 patients with glioblastomas showed that a high MIB-1 LI correlated with poor survival (P< 0.05). Among the molecules tested, only the low expression of S1P1was significantly correlated with the high MIB-1 LI in glioblastomas (P< 0.05). Multivariate analysis revealed that the S1P1expression level was a significant prognostic factor. Our results indicate that the MIB-1 LI is an important prognostic factor in human glioblastomas. Furthermore, downregulation of S1P1expression increases proliferative activity, and thus enhances the malignancy of glioblastomas, resulting in a poor survival.