MMP-9、CD44、TGF-β1在脑星形细胞瘤中应用研究

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目的MMP-9和CD44共同定位在细胞表面,且这种共同定位有助于CD44将MMP-9锚定于细胞表面并对胶原IV降解,促进肿瘤细胞的浸润。用可溶性CD44阻断CD44功能后即可使其丧失锚定MMP-9的作用。而被CD44锚定于细胞表面的MMP-9还可使无活性的TGF-β1前体活化,活化的TGF-β1则是新生血管生长所必需的生长因子。通过对CD44锚定的MMP-9及TGF-β1在脑星形细胞瘤中表达情况进行分析,对其表达意义进行研究,对CD44、MMP-9、TGF-β1在脑星形细胞瘤的浸润转移中的作用进行初步探讨,同时对CD44、MMP-9、TGF-β1相关性进行分析研究。方法共收集2006年郑州大学第一附属医院和许昌市中心医院手术切除的脑星形细胞瘤标本98例,应用免疫组化SP法检测肿瘤组织中CD44、MMP-9、TGF-β1的表达,分析CD44、MMP-9、TGF-β1和脑星形细胞瘤分级之间以及CD44、MMP-9、TGF-β1之间的关系。结果(1)CD44在星形细胞瘤组织中表达率77.55%(76/98),显著高于正常脑组织0(P<0.05)。通过Spearman等级相关检验,不同级别CD44表达具有统计学意义(r=0.95,P=0.046),星形细胞瘤级别与CD44阳性程度之间呈正相关。用Fishers精确检验法对不同级别进行检验,P=0.00027,说明不同级别之间CD44表达的构成比有差异性。(2)MMP-9在星形细胞瘤组织中表达率69.38%(68/98),显著高于正常脑组织(P<0.05)。通过Spearman等级相关检验,不同级别MMP-9表达具有统计学意义(r=0.89,P=0.038)。星形细胞瘤级别与MMP-9阳性程度之间呈正相关,用Fishers精确检验法对肿瘤4个级别MMP-9观察结果的构成情况进行检验,P=1.12×10-7。(3)TGF-β1在星形细胞瘤组织中表达率74.481%(73/98),显著高于正常脑组织(P<0.05)。通过Spearman等级相关检验,不同级别TGF-β1表达具有统计学意义(r=0.91,P=0.046)。星形细胞瘤级别与TGF-β1阳性程度之间呈正相关。用Fishers精确检验法对肿瘤4个级别TGF-β1观察结果的构成情况进行检验P=0.0001。(4)星形细胞瘤中CD44、MMP-9、TGF-β1表达的相关性分析CD44表达阳性的病例中,MMP-9的阳性表达率为94.12%,CD44表达阴性的病例中,MMP-9的阴性表达率为60.00%,CD44的表达和MMP-9表达之间呈正相关关系(列联系数rp=0.496016,P=1.559×10-8)。CD44表达阳性的病例中,TGF-β1的阳性表达率为82.89%,CD44表达阴性的病例中,TGF-β1的阴性表达率为54.55%,CD44的表达与TGF-β1表达呈正相关关系(列联系数rp=0.3136,P=0.001076)。MMP-9表达阳性的病例中,TGF-β1的阳性表达率为91.17%,MMP-9表达阴性的病例中,TGF-β1的阴性表达率为63.33%,经统计学分析表明MMP-9表达与TGF-β1表达呈正相关关系(列联系数rp=0.4825,P=4.93×10-8)。结论联合检测MMP-9、CD44、TGF-β1三者对脑星形细胞瘤的预后判断有重要意义。 The purpose of MMP-9 and CD44 co-localized on the cell surface, and this co-localization of CD44 will help MMP-9 anchored to the cell surface and collagen IV degradation, and promote tumor cell infiltration. With soluble CD44 block CD44 function can make it lose the role of anchoring MMP-9. MMP-9, which is anchored to the cell surface by CD44, also activates the inactive TGF-β1 precursor, which is an essential growth factor for neovascularization. By analyzing the expression of CD44-anchored MMP-9 and TGF-β1 in astrocytoma, the significance of expression of CD44, MMP-9 and TGF-β1 in astrocytoma Metastasis in the role of preliminary study, at the same time, CD44, MMP-9, TGF-β1 correlation analysis. Methods A total of 98 cases of brain astrocytoma were collected from the First Affiliated Hospital of Zhengzhou University and Central Hospital of Xuchang in 2006. The expressions of CD44, MMP-9 and TGF-β1 in the tumor tissue were detected by immunohistochemical SP method, The relationship between CD44, MMP-9, TGF-β1 and grade of astrocytoma as well as between CD44, MMP-9 and TGF-β1 was analyzed. Results (1) The expression of CD44 in astrocytoma was 77.55% (76/98), which was significantly higher than that in normal brain (P <0.05). Spearman rank correlation test showed that the expression of CD44 in different grades had statistical significance (r = 0.95, P = 0.046). There was a positive correlation between the level of astrocytoma and the positive degree of CD44. Different levels were tested using the Fishers exact test, P = 0.00027, indicating that there is a difference in the compositional ratio of CD44 between different grades. (2) The positive rate of MMP-9 in astrocytoma was 69.38% (68/98), which was significantly higher than that in normal brain tissue (P <0.05). The Spearman rank correlation test showed that the expression of MMP-9 in different grades had statistical significance (r = 0.89, P = 0.038). There was a positive correlation between the grade of astrocytoma and the positive degree of MMP-9. The Fishers exact test was used to test the formation of the tumor grade MMP-9, P = 1.12 × 10-7. (3) The expression of TGF-β1 in astrocytoma was 74.481% (73/98), which was significantly higher than that in normal brain tissue (P <0.05). By Spearman rank correlation test, different levels of TGF-β1 expression was statistically significant (r = 0.91, P = 0.046). There was a positive correlation between the level of astrocytoma and the positive degree of TGF-β1. The Fishers exact test was used to examine the constitution of the four levels of TGF-β1 in tumors with a test of P = 0.0001. (4) The correlation analysis of the expression of CD44, MMP-9 and TGF-β1 in astrocytoma The positive expression rate of MMP-9 in CD44 was 94.12%. Among the cases with negative CD44 expression, MMP-9 The negative expression rate of CD44 was 60.00%. There was a positive correlation between the expression of CD44 and MMP-9 (correlation coefficient rp = 0.496016, P = 1.559 × 10-8). The positive expression rate of TGF-β1 was 82.89% in CD44 positive cases and 54.55% in CD44 negative cases, and the expression of CD44 was positively correlated with the expression of TGF-β1 Number rp = 0.3136, P = 0.001076). The positive expression rate of TGF-β1 was 91.17% in cases with positive expression of MMP-9. The negative expression rate of TGF-β1 in cases with negative expression of MMP-9 was 63.33%. The statistical analysis showed that the expression of MMP- The positive expression of TGF-β1 (correlation coefficient rp = 0.4825, P = 4.93 × 10-8). Conclusion The combined detection of MMP-9, CD44, TGF-β1 in the prognosis of astrocytoma is of great significance.
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