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目的探讨Notch1胞内结构域(intracellular Domain,ICD)在星形细胞肿瘤中的表达规律及其临床意义。方法收集大坪医院2009年1-6月间经手术切除的12例不同级别星形细胞肿瘤及2例瘤周正常脑组织新鲜标本,采用实时定量PCR方法检测Notch1ICD mRNA表达;收集85例有完整随访资料的星形细胞肿瘤存档标本,采用免疫组织化学技术检测Notch1ICD蛋白表达。结果 Notch1ICD在正常脑组织中低或不表达,肿瘤组织中Notch1ICD mRNA水平(4.65±3.04)显著高于正常脑组织(1.13±0.11)(P<0.01);高级别(WHOⅢ和Ⅳ级)星形细胞肿瘤Notch1ICD mRNA表达水平显著高于低级别星形细胞肿瘤(WHOⅡ级)[分别为(6.58±2.63)与(2.49±1.01),P<0.01]。免疫组化结果显示,相对于瘤周正常脑组织,各级星形细胞肿瘤Notch1ICD表达明显增强,并由单纯胞质表达向胞质胞核联合表达及单纯胞核表达过渡;Notch1ICD蛋白表达与组织学分级及患者的存活期有关,Notch1ICD高表达预示着较高的组织学分级和较短的存活时间。结论 Notch信号通路的激活是星形细胞肿瘤的常见事件,Notch1ICD的异常表达与肿瘤分级及患者预后关系密切,可能成为胶质瘤基因治疗的有用分子靶标之一。
Objective To investigate the expression of Notch1 intracellular domain (ICD) in astrocytic tumors and its clinical significance. Methods 12 cases of astrocytoma and 2 cases of normal brain tissue were collected from Daping Hospital from January to June in 2009. The expression of Notch1ICD mRNA was detected by real-time PCR. A total of 85 cases with complete follow-up Data from astrocytoma archive specimens were used to detect Notch1 ICD protein expression by immunohistochemistry. Results The expression of Notch1ICD in normal brain tissue was significantly lower than that in normal brain tissue (4.65 ± 3.04 vs 1.13 ± 0.11, P <0.01) The expression level of Notch1ICD mRNA in tumor was significantly higher than that in low grade astrocytoma (6.58 ± 2.63 and 2.49 ± 1.01, P <0.01, respectively). The results of immunohistochemistry showed that the expression of Notch1ICD in astrocytic tumors at all stages was significantly increased compared with normal peri-tumor tissue, and the expression of Notch1ICD was significantly correlated with the expression of Notch1ICD The grade of learning and the patient’s survival were related to the high expression of Notch1ICD, which indicated higher histological grade and shorter survival time. Conclusion Activation of Notch signaling pathway is a common event in astrocytic tumors. Abnormal expression of Notch1ICD is closely related to tumor grade and prognosis, which may be one of the useful molecular targets for gene therapy of glioma.