CD105 (Endoglin) exerts prognostic effects via its role in the microvascular niche of paediatric high grade glioma.
CD105 (Endoglin) exerts prognostic effects via its role in the microvascular niche of paediatric high grade glioma.
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DOI：
10.1007/s00401-012-0952-1
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发表时间：
2012-07
影响因子：
12.7
通讯作者：
Grundy RG
中科院分区：
文献类型：
--
作者：
Smith SJ;Tilly H;Ward JH;Macarthur DC;Lowe J;Coyle B;Grundy RG
儿科高级别胶质瘤（pHGG）（世界卫生组织星形细胞瘤III级和IV级）仍然是预后不良的肿瘤，诊断后的中位生存期仅为15个月。目前的抗血管生成策略的研究主要集中在成人多形性胶质母细胞瘤（GBM），针对血管内皮生长因子的III期试验仍在继续。在这项研究中，我们调查了是否与pHGG（n = 150）的大队列预后血管的程度，以及是否不同的血管标记物进行不同的预后价值。我们发现，CD 105（endoglin）在多变量分析中与不良预后有显著相关性（p = <0.001）。全基因组基因表达数据的监督分层聚类确定了13个与队列中不同程度的血管分布相关的基因。通过实时聚合酶链反应验证了在该分析中鉴定的新的血管生成相关基因（包括MIPOL-1和ENPP 5）。我们还表明，CD 105阳性血管与CD 133阳性肿瘤细胞和CD 105阳性血管细胞的比例表明CD 133共阳性，这表明最近描述的血管生成拟态的现象发生在pHGG。总之，数据表明靶向血管生成，特别是CD 105，是pHGG的有效治疗策略。本文的在线版本（doi：10.1007/s 00401 -012-0952-1）包含补充材料，可供授权用户使用。
Paediatric high grade glioma (pHGG) (World Health Organisation astrocytoma grades III and IV) remains poor prognosis tumours, with a median survival of only 15 months following diagnosis. Current investigation of anti-angiogenic strategies has focused on adult glioblastoma multiforme (GBM) with phase III trials targeting vascular endothelial growth factor continuing. In this study we investigated whether the degree of vascularity correlated with prognosis in a large cohort of pHGG (n = 150) and whether different vessel markers carried different prognostic value. We found that CD105 (endoglin) had a strongly significant association with poor prognosis on multivariate analysis (p = <0.001). Supervised hierarchical clustering of genome wide gene expression data identified 13 genes associated with differential degrees of vascularity in the cohort. The novel angiogenesis-associated genes identified in this analysis (including MIPOL-1 and ENPP5) were validated by realtime polymerase chain reaction. We also demonstrate that CD105 positive blood vessels associate with CD133 positive tumour cells and that a proportion of CD105 positive vessel cells demonstrates co-positivity for CD133, suggesting that the recently described phenomenon of vasculogenic mimicry occurs in pHGG. Together, the data suggest that targeting angiogenesis, and in particular CD105, is a valid therapeutic strategy for pHGG. The online version of this article (doi:10.1007/s00401-012-0952-1) contains supplementary material, which is available to authorized users.
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影响因子：
3.8
作者：
Hockla A;Radisky DC;Radisky ES
通讯作者：
Radisky ES
人类胚胎干细胞，结肠癌和黑色素瘤细胞系中CD133表位的细胞周期依赖性变化。
影响因子：
11.2
作者：
Jaksch, Marie;Munera, Jorge;Bajpai, Ruchi;Terskikh, Alexey;Oshima, Robert G.
通讯作者：
Oshima, Robert G.
影响因子：
--
作者：
DOHRMANN, GJ;FARWELL, JR;FLANNERY, JT
通讯作者：
FLANNERY, JT
影响因子：
1.4
作者：
Germanò, A;Caffo, M;Tomasello, F
通讯作者：
Tomasello, F
影响因子：
82.9
作者：
Lebrin, Franck;Srun, Samly;Mummery, Christine L.
通讯作者：
Mummery, Christine L.