胶质瘤失活蛋白在星形细胞瘤中的表达及临床意义

Abnormal Expression of LGI1 Gene and its Clinical Significance in Astrocytoma

背景与目的:胶质瘤是最常见的恶性原发脑肿瘤,又以星形细胞瘤为最常见的胶质瘤。LGI1基因(leucine-rich glioma inactivated gene 1,LGI1)被发现在成神经胶质瘤细胞株上出现了基因重排现象,从而被认为是可以抑制肿瘤的候选基因,其结构和功能的异常将导致LGI1蛋白表达的缺失,可能是肿瘤细胞发生浸润转移和逃逸机体免疫监视的重要机制之一。本研究通过检测星形细胞瘤组织中胶质瘤失活蛋白的表达水平,探讨其与星形细胞瘤发生、发展、恶性程度及预后的关系。方法:应用免疫组织化学技术对50例星形细胞瘤患者肿瘤组织和12例来自于脑外伤内减压手术、高血压脑出血及脑血管畸形手术中所取的正常脑组织中LGI1蛋白的表达进行了检测。结果:肿瘤组与正常组LGI1蛋白阳性细胞百分率[(0.283±0.271)vs(0.573±0.229)比较有显著性差异(P<0.05);低级别星形细胞瘤和高级别胶质瘤中LGI1蛋白阳性细胞百分率[(0.383±0.279)vs(0.165±0.212)]比较有显著性差异(P<0.05)。50例星形细胞瘤患者中肿瘤复发组与未复发组的LGI1蛋白表达阳性率(8/27vs18/23)比较有显著性差异(P<0.05);死亡组与未死亡组中的LGI1蛋白表达阳性率(4/21vs22/29)比较有显著性差异(P<0.05)。50例星形细胞瘤患者中LGI1蛋白表达阳性组与表达阴性组GOS评分[(1.85±1.46)vs(3.92±1.64)比较有显著性差异(P<0.05)。结论:星形细胞瘤患者存在LGI1蛋白分子低表达,推测LGI1蛋白缺失率有可能成为预测脑胶质瘤恶性程度及预后的指标之一。

BACKGROUND ＆ OBJECTIVE：Glioma is the commonest primary cerebral malignant tumor. Astrocytoma is the commonest among gliomas. The leucine-rich glioma inactivated gene 1 （LGI1） has been found to be interrupted by a translocation breakpoint in a glioblastoma cell line . It was believed to be a candidate tumor suppressor gene. Abnormalities in structure and function of LGI1 lead to loss of extracellular matrix expression of LGI1 protein. This may be an important mechanism for tumor cells to escape from immune surveillance. So the objectives of present study was to examine the expression of LGI1 protein by SP immunohistochemical analysis. We discussed the correlation between LGI1 protein and pathological grade, rate of relapse and prognosis of glioma, and investigated the value of LGI1 in evaluating malignancy and predicting prognosis. METHODS： All the tissue samples from 50 astrocytoma cases （tumor group） and 12 cases （normal group） of cerebral trauma with intracranial decompression, or hypertensive intracerebral hemorrhage or cerebral vesenlar malformation were hydrated through graded alcohols, then the antigen were repaired by microwave, and the expression of LGI1 protein were determined by SP immunohistochemical analysis. RESULTS： Among the 50 cases with astrocytoma, 26 cases were positive in the LGI1 protein expression and the percentage of LGI1 protein was 0.283±0.2711; All 12 normal cases were positive in expression and the percentage of LGI1 protein was 0.573± 0.2293. Expression of LGI1 showed significant difference between the tumor group and the normal group （P〈 0.05）. The percentage of LGI1 protein was 0.383±0.2786 in 27 cases of low-grade（ Ⅰ or Ⅱ ） astrocytoma and it was 0.165±0.2123 in 23 cases of high-grade（Ⅲ or Ⅳ） astrocytoma. Statistical significance was found among them （P〈0.05）. Twenty cases of positive LGI1 protein expression were identified in 27 cases with low-grade astrocytoma. Only 6 cases were positive in expression in 23 cases with high-grade astrocytoma （P〈0.05）. Among 27 relapse cases, 8 cases were positive in LGI1 expression, which was much lower （P〈0.05） than those in non-relapse group （18/23）. Among the 50 cases, 4 cases were positively expressed in 21 dead cases while 22 cases were positively expressed in 29 survival cases （P〈0.05）. CONCLUSION： The expression of LGI1 protein decreased with higher pathological grade of astrocytoma. The low expression of LGI1 protein in astrocytoma may escape from immunological surveillance in pathogenesis. LGI1 protein may act as a marker in evaluating histological grading and prognosis of astrocytoma.