基质金属蛋白酶1／蛋白酶活性受体-1信号通路在胶质瘤发展中的作用

Upregulation of matrix metalloproteinase-1 and proteinase-activated receptor-1 promotes the progression or- human gliomas

目的探讨基质金属蛋白酶l／蛋白酶活性受体-l（MMP-1／PARl）信号通路在脑胶质瘤发展的作用及其意义。方法应用免疫组织化学方法检测108例原发性胶质瘤患者肿瘤组织中MMP．1和PARl的表达模式。采用Kaplan．Meier生存分析和Cox比例风险模型分析胶质瘤患者的预后。结果免疫染色结果显示108例患者活体组织有83．3％表达MMP-1（90／108），76．9％表达PARl（83／108）。PARl的表达与MMP．1的表达显著相关（r=0．8，P〈0．01）。高级别胶质瘤MMP-1和PARl的免疫组织化学（IHC）总分明显高于低级别胶质瘤（两者P〈0．01）。此外，MMP-1和PARl表达高的患者Krnofsky行为能力（KPS）评分低于MMP-1和PARl表达低的患者（两者P〈0．01）。而且，患者总体生存率降低的结果表明，MMP-1和PARl表达情况是胶质瘤的强预后指标（P〈0．01）。多因素Cox分析显示KPS（P〈0．01）、WHO病理分级（P〈0．01）、MMP-1（P〈0．01）和PARl（P〈0．01）是影响脑胶质瘤预后的独立因素。结论脑胶质瘤中MMP-1／PARl信号通路的活化与肿瘤恶性程度及临床结果相关。

Objective To investigate the effect of matrix metalloproteinase-1 （MMP-1） and pro- teinase-activated receptor-1 （PAR1） on the progression of human gliomas. Methods Immunohistochemi- cal staining was performed to detect the expression patterns of MMP-1 and PAR1 in biopsies from 108 pa- tients with primary gliomas. Kaplan-Meier survival and Cox regression analyses were done to evaluate the prognosis of patients. Results Immunostaining revealed MMP-1 to be expressed in 83.3% （90/108） and PAR1 in 76. 9% （83/108） of the biopsies respextively. PAR1 expression was significantly correlated with that of MMP-1 （r = 0. 8 ,P 〈 0. 01 ）. The total immunohistochemistry （IHC） scores for MMP-1 and PAR1 were significantly higher in high-grade tumors than in low-grade tumors （both P 〈 0. 01 ）. In addition, pa- tients with high MMP-1 and high PAR1 expression had lower Karnofsky performance scale （KPS） scores than those with low MMP-1 and low PAR1 expression （both P 〈0. 01）. Moreover, MMP-1 and PAR1 ex- pression was shown to be a strong prognostic marker for decreased overall survival （P 〈 O. 01, respective- ly）. Furthermore, Cox multi-factor analysis showed that KPS （ P 〈 0. O1 ）, WHO grade （ P 〈 O. O1 ）, MMP-1 （P 〈0. O1 ）, and PAR1 （P 〈0.01 ） were independent prognostic factors for human gliomas. Con- clusion Our results suggest that in gliomas, the upregulation of MMP-1 and PAR1 correlates with histo- logical malignancy ~rade and clinical outcome.