Serum angiogenic profile of patients with glioblastoma identifies distinct tumor subtypes and shows that TIMP-1 is a prognostic factor
Serum angiogenic profile of patients with glioblastoma identifies distinct tumor subtypes and shows that TIMP-1 is a prognostic factor
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DOI：
10.1093/neuonc/noq170
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发表时间：
2011-01-01
期刊：
影响因子：
15.9
通讯作者：
Papadopoulos, Marios C.
中科院分区：
文献类型：
--
作者：
Crocker, Matthew;Ashley, Sue;Papadopoulos, Marios C.
血管生成在胶质母细胞瘤生物学中起着关键作用，抗血管生成药物正在临床研究中，结果令人鼓舞。然而，胶质母细胞瘤患者的血管生成特征及其临床意义还不清楚。在这里，我们描述了胶质母细胞瘤患者的血管生成特征，并研究了单个血管生成因子的预后意义。收集了36例胶质母细胞瘤患者入院时的血清样本，并使用蛋白质微阵列同时测定了48种血管生成因子。数据分析采用层次聚类分析。血管形态进行了评估后，泛内皮标记物CD 31免疫染色的组织学。还对肿瘤样品进行金属蛋白酶组织抑制剂-1（TIMP-1）的免疫染色。血清血管生成谱的聚类分析揭示了胶质母细胞瘤的2种不同亚型。2种亚型肿瘤微血管密度差异显著。TIMP-1的低浓度水平与显著延长的生存期相关，与患者年龄、体力状态或治疗无关。胶质母细胞瘤患者的血清血管生成谱反映了肿瘤生物学，并具有预后价值。我们的数据表明，血清TIMP-1水平作为一个独立的预测生存。
Angiogenesis plays a key role in glioblastoma biology and antiangiogenic agents arc under clinical investigation with promising results. However, the angiogenic profiles of patients with glioblastoma and their clinical significance are not well understood. Here we characterize the scrum angiogenic profile of patients with glioblastoma, and examine the prognostic significance of individual angiogenic factors. Serum samples from 36 patients with glioblastoma were collected on admission and simultaneously assayed for 48 angiogenic factors using protein microarrays. The data were analyzed using hierarchical cluster analysis. Vessel morphology was assessed histologically after immunostaining for the pan-endothelial marker CD31. Tumor samples were also immunostained for tissue inhibitor of metalloproteinase-1 (TIMP-1). Cluster analysis of the serum angiogenic profiles revealed 2 distinct subtypes of glioblastoma. The 2 subtypes had markedly different tumor microvessel densities. A low scrum level of TIMP-1 was associated with significantly longer survival independent of patient age, performance status, or treatment. The serum angiogenic profile in patients with glioblastoma mirrors tumor biology and has prognostic value. Our data suggest the serum TIMP-1 level as an independent predictor of survival.