脑胶质瘤患者尿激酶型纤溶酶原激活因子基因的表达

Expression of urokinase type plasminogen activator gene in patients with brain gliomas

目的 研究尿激酶型纤溶酶原激活因子 (u PA)与人脑胶质瘤恶性生物学行为的关系 .方法 采用 Northern印迹分子杂交和免疫组化方法检测 43例人脑胶质瘤和 5例正常脑组织 u PA m RNA及蛋白的表达 ,并与临床生物学参数进行综合分析 .结果 上述组织或细胞均表达 2 .5 kb的 u PA m R-NA转录物 ,高级别胶质瘤较低级别和正常脑组织 u PA m R-NA表达水平明显增高 (P<0 .0 1 ) ,但低级别胶质瘤和正常脑组织 u PA m RNA表达水平无明显差异 (P>0 .0 5 ) .术后 1 8mo内复发和生存期小于 3a者 u PA m RNA表达显著高于术后 1 8mo无复发及生存期大于 3a者 (P<0 .0 1 ) ;靠近坏死区域的瘤细胞亦有 u PA m RNA表达 ,u PA m RNA表达水平与胶质瘤微血管数量呈正相关 (r=0 .5 6 ,P<0 .0 1 ) ,而与患者性别、年龄及肿瘤大小则无显著相关 .u PA蛋白主要分布在胶质母细胞瘤、间变性星形细胞瘤组织的瘤细胞及内皮细胞 ,低级别胶质瘤较少 .结论 u PA基因表达可能与胶质瘤的恶性发展有关 。

AIM To investigate the relationship between urokinase type plasminogen activator (uPA) activity and the malignant biological behavior of human gliomas. METHODS The amounts of uPA were measured by Northern blotting hybridization and immunohistochemical method in 43 cases of brain gliomas and 5 cases of normal brain tissues, and their relation to the clinical indexes was comprehensively analyzed. RESULTS All tissues expressed 2.5 kb transcripts of uPA mRNA. The uPA mRNA level were significantly higher in high grade gliomas than in low grade gliomas and normal brain tissues ( P <0.01), but no significant difference was observed between low grade gliomas and normal brain tissues ( P >0.05) . Levels of uPA mRNA expression in tumor tissues with recurrence in 18 months postoperatively and survival period less than 3 years were significantly higher than their counterparts ( P <0.01). The uPA mRNA was also expressed in tumor cells near necrotic areas. uPA mRNA expression was considerably correlated with the microvessel quantity (MVQ) in gliomas ( r =0.56, P <0.01), but had no significant correlation with the sex or age of the patients and tumor size . The distribution of uPA protein was mainly in tumor cells and endothelial cells of glioblastomas and anaplastic astrocytomas, whereas it was almost undetectable in low grade gliomas. CONCLUSION The expression of uPA gene is associated with the malignant progression of gliomas and plays an important role in the recurrence and invasive behaviors of high grade gliomas.