Liang Jianfeng, Tong Pan, Zhao Wanni, Li Yaqiao, Zhang Li, Xia Ying, Yu Yanbing
Department of Neurosurgery, China-Japan Friendship Hospital, Beijing 100029, China.
Department of Bioinformatics and Computational Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Int J Mol Sci. 2014 Jun 25;15(7):11220-33. doi: 10.3390/ijms150711220.
Neuroblastoma is the most common and deadly solid tumor in children, and there is currently no effective treatment available for neuroblastoma patients. The repressor element-1 silencing transcription (REST) factor has been found to play important roles in the regulation of neural differentiation and tumorigenesis. Recently, a REST signature consisting of downstream targets of REST has been reported to have clinical relevance in both breast cancer and glioblastoma. However it remains unclear how the REST signature works in neuroblastoma. Publicly available datasets were mined and bioinformatic approaches were used to investigate the utility of the REST signature in neuroblastoma with both preclinical and real patient data. The REST signature was found to be associated with drug sensitivity in neuroblastoma cell lines. Further, neuroblastoma patients with enhanced REST activity are significantly associated with higher clinical stages. Loss of heterozygosity on chromosome 11q23, which occurs in a large subset of high-risk neuroblastomas, tends to be correlated with high REST activity, with marginal significance. In conclusion, the REST signature has important implications for targeted therapy, and it is a prognostic factor in neuroblastoma patients.
神经母细胞瘤是儿童中最常见且致命的实体瘤，目前神经母细胞瘤患者尚无有效的治疗方法。已发现阻遏元件-1沉默转录（REST）因子在神经分化和肿瘤发生的调控中发挥重要作用。最近，据报道，由REST下游靶点组成的REST特征在乳腺癌和胶质母细胞瘤中均具有临床相关性。然而，REST特征在神经母细胞瘤中如何发挥作用仍不清楚。我们挖掘了公开可用的数据集，并使用生物信息学方法，利用临床前和真实患者数据研究REST特征在神经母细胞瘤中的效用。发现REST特征与神经母细胞瘤细胞系中的药物敏感性相关。此外，REST活性增强的神经母细胞瘤患者与更高的临床分期显著相关。11q23染色体上的杂合性缺失在很大一部分高危神经母细胞瘤中出现，往往与高REST活性相关，具有边缘显著性。总之，REST特征对靶向治疗具有重要意义，并且是神经母细胞瘤患者的一个预后因素。
