title: Upregulation of matrix metalloproteinase-1 and proteinase-activated receptor-1 promotes the progression of human gliomas.
abstract: 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.
authors.affiliation: Department of Neurosurgery, the Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212001 Jiangsu, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Zhan
authors.forename: Wenlin
authors.initials: W
authors.lastname: Xu
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Yuan
authors.forename: Peisong
authors.initials: P
authors.lastname: Lu
authors.forename: Liping
authors.initials: L
authors.lastname: Zhan
authors.forename: Qiaoyu
authors.initials: Q
authors.lastname: Li
mesh_terms: D001706:Biopsy; D001932:Brain Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005910:Glioma / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D044463:Receptor, PAR-1 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D044463:Receptor, PAR-1; D020781:Matrix Metalloproteinase 1