胶质母细胞瘤组织Asporin表达变化及其与患者替莫唑胺耐药、预后的关系

Expression of Asporin in glioblastoma tissues and its relationship with temozolomide resistance and prognosis

目的观察胶质母细胞瘤(GBM)组织中牙周韧带相关蛋白-1(Asporin)的表达变化,并分析其与患者替莫唑胺(TMZ)耐药、预后的关系。方法选取GBM组织40例份,正常脑组织10例份,采用Western blotting法和免疫组化法检测各脑组织Asporin,根据Asporin的表达情况将GBM标本分为高表达者和低表达者,分析Asporin表达与患者对TMZ耐药性、预后的关系。结果 GBM组织、正常脑组织Asporin相对表达量分别为1.90±1.20、0.34±0.20,免疫组化染色得分分别为(8.01±4.38)、(2.00±1.15)分,两者比较,P均<0.05。接受MGMT启动子甲基化检测的17例GBM患者中,12例MGMT启动子未甲基化(对TMZ耐药),5例MGMT启动子甲基化(对TMZ敏感),12例对TMZ耐药者、5例对TMZ敏感者瘤组织Asporin相对表达量分别为3.07±0.61、1.04±0.18,两者比较,P<0.05;接受MGMT启动子甲基化检测的17例GBM患者根据瘤组织免疫组化染色评分结果分为Asporin高表达者(13例)、Asporin低表达者(4例),Asporin高、低表达者中对TMZ耐药者分别为10、2例,两者比较,P<0.05。30例GBM患者根据瘤组织Asporin染色评分结果分为高表达者(27例)、低表达者(13例),Asporin高、低表达者中位生存期分别为(12.0±0.7)、(23.0±3.9)个月,两者比较,P<0.05。结论 GBM组织Asporin的表达升高,Asporin表达水平越高,对TMZ耐药者越多,患者预后越差。

Objective To observe the expression changes of Asporin in the glioblastoma(GBM) tissues,and to analyze its relationship with the temozolomide(TMZ) resistance and prognosis of patients.Methods Forty cases of GBM tissues and 10 cases of normal brain tissues were selected.Western blotting and immunohistochemistry were used to detect Asporin in each brain tissue.According to the expression of Asporin,GBM specimens were divided into the high expressors and low expressors.We analyzed the relationship between Asporin expression and patients’ resistance to TMZ and prognosis.Results The relative expression levels of Asporin in the GBM tissues and normal brain tissues were 1.90±1.20 and 0.34±0.20,respectively;the immunohistochemical staining scores were(8.01±4.38) and(2.00±1.15)points,respectively,with statistically significant difference between these two groups(all P<0.05).Among 17 GBM patients who underwent MGMT promoter methylation test,12 patients did not have MGMT promoter methylation(resistant to TMZ),and 5 patients had MGMT promoter methylation(sensitive to TMZ).The relative expression of Asporin in the drugresistant and sensitive patients’ tumor tissues was 3.07±0.61 and 1.04±0.18,respectively,with statistically significant difference between these two groups(P<0.05).According to the immunohistochemical staining scores of tumor tissues,17 GBM patients who underwent MGMT promoter methylation test were divided into patients with high Asporin expression(13 cases) and those with low Asporin expression(4 cases).The number of resistant cases to TMZ was 10 and 2,respectively,with statistically significant difference between these two groups(P<0.05).According to the Asporin staining score of tumor tissues,30 GBM patients were divided into 27 cases of patients with high expression and 13 cases of patients with low expression.The median survival time was(12.0±0.7) and(23.0±3.9) months,respectively,with statistically significant difference between these two groups(P<0.05).Conclusions The expression of Asporin in the GBM tissues increases.The higher the level of Asporin expression,the more resistant to TMZ,and the worse the prognosis of patients.