微管相关蛋白LC3B-Ⅱ和自噬基因Beclin 1在星形细胞肿瘤中的表达及其意义

Expressions of microtubule-associated protein 1 light chain 3B and autophagy-related geneBeclin 1 and their clinical significance in astrocytic tumors

目的探讨微管相关蛋白1轻链3B（MAP1-LC3B）和自噬相关基因BeclinJ在星形细胞肿瘤中的表达及其与星形细胞肿瘤病理和临床表现的相关性及意义。方法选择上海长征医院神经外科2006年1月至2006年12月住院手术治疗的初发性星形细胞肿瘤患者62例，其中Ⅰ级（毛细胞性星形细胞瘤）4例，Ⅱ级（星形细胞瘤）23例，Ⅲ级（间变性星形细胞瘤）12例，Ⅳ级（胶母细胞瘤）23例。免疫组织化学染色检测肿瘤标本中Beclin 1的表达，免疫印迹法检测Beclin1和MAP1-LC3B的表达并统计Beclin 1、MAP1-LC3B的表达与星形细胞肿瘤临床病理表现的关系。结果免疫组化显示I～Ⅳ级星形细胞肿瘤中Beclin1的表达随肿瘤级别的升高而降低，差异有统计学意义（氏0．05）。免疫印迹检测结果显示不同病理分级、生存期患者Beclin 1的表达差异有统计学意义（P〈0．05），不同病理分级患者MAP1-LC3B．Ⅱ表达的差异有统计学意义（P〈0．05）；相关性分析显示MAP1-LC3B-Ⅱ、Beclin1在星形细胞肿瘤中的表达与病理分级呈负相关关系（r=0．334，p=0．007；r=-0．448，P=-0．000），MAPI—LC3B-Ⅱ、Beclin1在星形细胞肿瘤中的表达与生存时间呈正相关关系（r==0．285，P=0．027；r=0．359，P=-0．005）。MAP1-LC3B．Ⅱ和Beclin1的表达之间也呈正相关关系（r=0．272．P=0．035）。结论MAP1-LC3B．Ⅱ和Beclin1在胶母细胞瘤中的表达下调，自噬活性的改变可能与星形细胞肿瘤的发生、发展相关。

Objective To investigate the expressions of microtubule -associated protein 1 （MAP1） light chain 3B （LC3B） and autophagy-related gene Beclinl in astrocytic tumors, and explore their correlations with the pathological features and clinical manifestations of astrocytic tumors to further reveal their roles in tumorigenesis and development of astrocytic tumors. Methods Sixty-two specimens with different-grade astrocytic tumors, including 4 with grade I （pilocytic astrocytoma）, 23 with grade II （astrocytoma）, 12 with grade III （anaplastic astrocytoma） and 23 with grade IV （glioblastoma multiforme）, were selected in our study. Immunohistochemistry was employed to detect the expression of Beclin 1; the expressions of MAP 1-LC3B and Beclin 1 were detected by Western blotting. The correlations between expressions of MAP1-LC3B and Beclinl and both the pathological features and clinical manifestations of astrocytic tumors were analyzed. Results Immunohistochemistry showed decreased Beclinl expression in the astrocytic tumors following the increase of tumor grades （P〈0.05）. Western blotting indicated that the expressions of Beclinl in tumors with different grades and these patients with different life cycles were significantly different （P〈0.05） and the average optical densityratio of Beclinl in high-grade astrocytic tumors （grade Ⅲ/Ⅳ） was obviously lower than that in low-grade astrocytic tumors （grade Ⅰ/Ⅱ, P〈0.05）. The expressions of LC3B-I showed significant differences in different-grade astrocytic tumors, and the expression of LC3B-I of grade IV tumor was statistically lower than that of grade I, II and III tumors（P〈0.05）. The expressions of LC3B-II and Beclin 1 were negatively correlated to the pathological grade of the tumors （r=-0.334, P=-0.007; r=-0.448, P=-0.000）, but positively correlated to the survival time（r=0.285, P=0.027; r=0.359, P=-0.005）. The expressions of LC3B-Ⅱ and Beclin 1 had a positive correlation （r=0.272, P=-0.035）. Conclusion Expressions of LC3B-II and Beclinl are down-regulated in glioblastoma multiforme; the decrease of autophagic capacity may relate to the tumorigenesis and development of astrocytic tumors.