Jessica L. Bell, Raseswari Turlapati, and Stefan Hüttelmaier, Martin Luther University Halle-Wittenberg, Halle; Johannes H. Schulte, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, and University Children's Hospital Essen, Essen; Johannes H. Schulte, German Cancer Consortium and German Cancer Research Center, Heidelberg, Germany; and Tao Liu, Children's Cancer Institute Australia for Medical Research and University of New South Wales, Randwick, New South Wales, Australia.
J Clin Oncol. 2015 Apr 10;33(11):1285-93. doi: 10.1200/JCO.2014.55.9880. Epub 2015 Mar 9.
Chromosomal 17q21-ter gain in neuroblastoma is both a common and prognostically significant event. The insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1) gene is located near the proximal edge of this region. Here, its prognostic value is evaluated in neuroblastoma.
The mRNA expression of IGF2BP family members was first evaluated by microarray data sets. In addition, in a separate cohort of 69 tumors, IGF2BP1 gene copy number, mRNA, and protein abundance were determined and compared with clinical parameters.
In two independent microarray data sets, 77% to 100% of tumors had substantial IGF2BP1 mRNA levels measured. High IGF2BP1 transcript abundance was significantly associated with stage 4 tumors (P < .001) and decreased patient survival (P < .001). IGF2BP1 was also associated with MYCN gene amplification and MYCN mRNA abundance. In the 69 neuroblastoma samples, IGF2BP1 DNA copy number (increased in 84% of tumors), mRNA, and protein abundance were significantly higher in stage 4 compared with stage 1 tumors. Importantly, IGF2BP1 protein levels were associated with lower overall patient survival (P = .012) and positively correlated with MYCN mRNA, even when excluding MYCN-amplified tumors. Moreover, IGF2BP1 clearly affected MYCN expression and neuroblastoma cell survival in vitro.
In neuroblastoma, IGF2BP1 was expressed in the majority of neuroblastoma specimens analyzed and was associated with lower overall patient survival and MYCN abundance. These data demonstrate that IGF2BP1 is a potential oncogene and an independent negative prognostic factor in neuroblastoma.
神经母细胞瘤 17q21 端获得性染色体增益是一种常见且具有显著预后意义的事件。胰岛素样生长因子 2mRNA 结合蛋白 1（IGF2BP1）基因位于该区域的近端边缘。在此，评估其在神经母细胞瘤中的预后价值。
首先通过微阵列数据集评估 IGF2BP 家族成员的 mRNA 表达。此外，在另一批 69 例肿瘤中，确定 IGF2BP1 基因拷贝数、mRNA 和蛋白丰度，并与临床参数进行比较。
在两个独立的微阵列数据集，77%至 100%的肿瘤中 IGF2BP1 mRNA 水平显著升高。高 IGF2BP1 转录丰度与 4 期肿瘤显著相关（P<.001），并降低患者生存率（P<.001）。IGF2BP1 还与 MYCN 基因扩增和 MYCN mRNA 丰度相关。在 69 例神经母细胞瘤样本中，IGF2BP1 DNA 拷贝数（84%的肿瘤增加）、mRNA 和蛋白丰度在 4 期肿瘤中显著高于 1 期肿瘤。重要的是，IGF2BP1 蛋白水平与整体患者生存率降低相关（P=0.012），并且与 MYCN mRNA 呈正相关，即使排除 MYCN 扩增肿瘤。此外，IGF2BP1 明显影响 MYCN 表达和神经母细胞瘤细胞体外存活。
在神经母细胞瘤中，IGF2BP1 在分析的大多数神经母细胞瘤标本中表达，并与整体患者生存率降低和 MYCN 丰度相关。这些数据表明 IGF2BP1 是神经母细胞瘤中的潜在癌基因和独立的负预后因素。
