Rhabdomyosarcomas utilize developmental, myogenic growth factors for disease advantage: A report from the Children's Oncology Group
Rhabdomyosarcomas utilize developmental, myogenic growth factors for disease advantage: A report from the Children's Oncology Group
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DOI：
10.1002/pbc.20466
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发表时间：
2006-03-01
影响因子：
3.2
通讯作者：
Keller, C
中科院分区：
文献类型：
--
作者：
Blandford, MC;Barr, FG;Keller, C
背景。不可切除或转移性疾病是治疗横纹肌肉瘤儿童的最大障碍。在这项研究中，我们试图确定晚期和进展性疾病的基因表达特征。程序。通过对一组集中的 60 个基因进行寡核苷酸基因表达分析，我们分析了来自组间横纹肌肉瘤研究 IV 的 89 个横纹肌肉瘤的肌源性表达谱。结果。虽然横纹肌肉瘤的表达谱与正常胚胎肌源性祖细胞的基因表达谱非常相似，但生长因子与疾病进展关系最为密切。具体来说，我们发现血小板衍生生长因子（PDGF）受体和胰岛素样生长因子与无失败生存率下降密切相关。独立数据集的实时逆转录聚合酶链式反应（RT-PCR）表明，自分泌生长信号如果存在，则不会在转录水平上以简单的方式受到调节。结论。 PDGF 受体和胰岛素样生长因子转录水平的增加与横纹肌肉瘤的生存率降低有关。双重阻断这些生长因子信号通路可能是临床前治疗研究中的一个有价值的策略。
Background. Unresectable or metastatic disease represents the greatest obstacle to cure for children with rhabdomyosarcoma. in this study we sought to identify gene expression signatures of advanced stage and progressive disease. Procedure. Using oligonucleotide gene expression analysis for a focused set of 60 genes, we analyzed the myogenic expression profiles of 89 rhabdomyosarcomas from the Intergroup Rhabdomyosarcoma Study-IV. Results. While the expression profile of rhabdomyosarcomas closely paralleled gene expression profiles of normal embryonic myogenic progenitors, growth factors were most closely associated with disease progression. Specifically, we identified platelet-derived growth factor (PDGF) receptors and insulin-like growth factor as strongly correlated with decreased failure-free survival. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) of an independent data set suggested that autocrine growth signaling, if present, is not regulated in a simple manner at the transcriptional level. Conclusions. increased transcriptional levels of PDGF receptors and insulin-like growth factor are associated with decreased survival in rhabdomyosarcomas. Dual blockade of these growth-factor-signaling pathways may be a valuable strategy in preclinical therapeutic Studies.