Comparative Analysis of Matrix Metalloproteinase Family Members Reveals That MMP9 Predicts Survival and Response to Temozolomide in Patients with Primary Glioblastoma.
Comparative Analysis of Matrix Metalloproteinase Family Members Reveals That MMP9 Predicts Survival and Response to Temozolomide in Patients with Primary Glioblastoma.
复制标题
基质金属蛋白酶家族成员的比较分析表明，MMP9 可以预测原发性胶质母细胞瘤患者的存活率和对替莫唑胺的反应。
DOI：
10.1371/journal.pone.0151815
复制
发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Jiang C
中科院分区：
文献类型：
--
作者：
Li Q;Chen B;Cai J;Sun Y;Wang G;Li Y;Li R;Feng Y;Han B;Li J;Tian Y;Yi L;Jiang C
多形性胶质母细胞瘤(GBM)是成人最常见的原发恶性脑肿瘤。放射治疗加上同期和辅助的TMZ化疗是目前治疗GBM患者的标准治疗。基质金属蛋白酶(MMPs)是一类锌依赖的内肽酶家族，由于其降解ECM的能力，是肿瘤侵袭和转移的关键调节因子。本研究的目的是确定在预后和预测能力方面对原发性GBM患者信息量最大的基质金属蛋白酶成员。从中国脑胶质瘤基因组图谱数据库(CGGA)、分子脑肿瘤数据库(Rbra)和GSE16011数据库中获取所有基质金属蛋白酶基因的表达谱。通过焦磷酸测序检测MGMT甲基化状态。探讨MMP9在各级别胶质瘤标本中的表达与肿瘤进展的关系。采用Kaplan-Meier分析和Cox比例风险回归模型分析MMP9表达与生存期和替莫唑胺疗效的关系。在原发胶质母细胞瘤患者的三个数据集中，MMP9是唯一有意义的预后因素。我们的结果表明，MMP9的表达与胶质瘤的分级有关(p<；0.0001)。此外，MMP9的低表达与较好的预后相关(OS：P=0.0012和PFS：P=0.0066)，并且MMP9是原发基底膜的独立预后因素(OS：P=0.027和PFS：P=0.032)。此外，无论MGMT甲基化状态如何，MMP9低表达的GBM患者均受益于替莫唑胺(TMZ)化疗。MMP9低表达的原发基底膜患者可能有更长的生存期，并可能受益于替莫唑胺化疗。
Glioblastoma multiform (GBM) is the most common malignant primary brain tumor in adults. Radiotherapy plus concomitant and adjuvant TMZ chemotherapy is the current standard of care for patients with GBM. Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, are key modulators of tumor invasion and metastasis due to their ECM degradation capacity. The aim of the present study was to identify the most informative MMP member in terms of prognostic and predictive ability for patients with primary GBM. The mRNA expression profiles of all MMP genes were obtained from the Chinese Glioma Genome Atlas (CGGA), the Repository for Molecular Brain Neoplasia Data (REMBRANDT) and the GSE16011 dataset. MGMT methylation status was also examined by pyrosequencing. The correlation of MMP9 expression with tumor progression was explored in glioma specimens of all grades. Kaplan–Meier analysis and Cox proportional hazards regression models were used to investigate the association of MMP9 expression with survival and response to temozolomide. MMP9 was the only significant prognostic factor in three datasets for primary glioblastoma patients. Our results indicated that MMP9 expression is correlated with glioma grade (p<0.0001). Additionally, low expression of MMP9 was correlated with better survival outcome (OS: p = 0.0012 and PFS: p = 0.0066), and MMP9 was an independent prognostic factor in primary GBM (OS: p = 0.027 and PFS: p = 0.032). Additionally, the GBM patients with low MMP9 expression benefited from temozolomide (TMZ) chemotherapy regardless of the MGMT methylation status. Patients with primary GBMs with low MMP9 expression may have longer survival and may benefit from temozolomide chemotherapy.