Department of Neurosurgery, the Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212001 Jiangsu, China.
Pathol Res Pract. 2011 Jan 15;207(1):24-9. doi: 10.1016/j.prp.2010.10.003. Epub 2010 Nov 18.
Matrix metalloproteinases (MMPs) have been proposed to be involved in remodeling the tumor-stromal microenvironment. The protease-activated receptors (PARs) are the latest MMP targets. Recent studies have revealed that stromal-derived MMP-1 acts as a signaling molecule by cleaving PAR1 to cause tumor migration and invasion of various cancers. However, the involvement of MMP-1/PAR1 signaling pathway in the progression and prognosis of human gliomas remains to be identified. Immunohistochemical staining was performed to detect the expression patterns of MMP-1 and PAR1 in biopsies from 108 patients with primary gliomas. Kaplan-Meier survival and Cox regression analyzes were performed to evaluate the prognosis of patients. Immunostaining revealed MMP-1 to be expressed in 83.3% (90/108) and PAR1 in 76.9% (83/108) of the biopsies. PAR1 expression was significantly correlated with that of MMP-1 (r = 0.786, p<0.0001). The total IHC scores for MMP-1 and PAR1 were significantly higher in high-grade tumors than in low-grade tumors (both p = 0.001). In addition, patients with high MMP-1 and high PAR1 expression have lower Karnofsky performance scale (KPS) scores than patients with low MMP-1 and low PAR1 expression (both p = 0.008). Moreover, MMP-1 and PAR1 expression was shown to be a strong prognostic marker for decreased overall survival (p = 0.002 and 0.003, respectively). Furthermore, Cox multi-factor analysis showed that KPS (p = 0.008), WHO grade (p = 0.006), MMP-1 (p = 0.006), and PAR1 (p = 0.008) were independent prognostic factors for human gliomas. Our results suggest that in gliomas, the upregulation of MMP-1 and PAR1 correlates with histological malignancy grade and clinical outcome. Also, MMP-1 and PAR1 immunostaining supplements the current histological grading by offering additional prognostic and predictive information.
基质金属蛋白酶(MMPs)被认为参与重塑肿瘤基质微环境。蛋白酶激活受体(PARs)是 MMP 的最新靶标。最近的研究表明,基质衍生的 MMP-1 通过切割 PAR1 作为信号分子发挥作用,导致各种癌症的肿瘤迁移和侵袭。然而,基质金属蛋白酶-1/蛋白酶激活受体 1 信号通路在人类脑胶质瘤的进展和预后中的参与仍有待确定。进行免疫组织化学染色以检测 108 例原发性脑胶质瘤活检中 MMP-1 和 PAR1 的表达模式。进行 Kaplan-Meier 生存和 Cox 回归分析以评估患者的预后。免疫组化染色显示 MMP-1 在 83.3%(90/108)的活检中表达,PAR1 在 76.9%(83/108)的活检中表达。PAR1 表达与 MMP-1 表达显著相关(r=0.786,p<0.0001)。高级别肿瘤的 MMP-1 和 PAR1 的总免疫组化评分明显高于低级别肿瘤(均 p=0.001)。此外,高 MMP-1 和高 PAR1 表达的患者的卡诺夫斯基表现量表(KPS)评分低于低 MMP-1 和低 PAR1 表达的患者(均 p=0.008)。此外,MMP-1 和 PAR1 的表达被证明是总生存期降低的强预后标志物(p=0.002 和 0.003)。此外,Cox 多因素分析显示 KPS(p=0.008)、世界卫生组织分级(p=0.006)、MMP-1(p=0.006)和 PAR1(p=0.008)是人类脑胶质瘤的独立预后因素。我们的研究结果表明,在脑胶质瘤中,MMP-1 和 PAR1 的上调与组织学恶性程度和临床结果相关。此外,MMP-1 和 PAR1 免疫组化通过提供额外的预后和预测信息,补充了当前的组织学分级。