Abstract
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.
Highlights
Neuroblastoma is the most common pediatric malignancy in children, accounting for approximately15% of all cancer-related pediatric deaths [1,2,3]
This paper demonstrates that the Repressor element-1 silencing transcription (REST) signature applied well in both cell lines and neuroblastoma patients
17 of the 24 REST signature genes were available in neuroblastoma cell line data and 15 of them were in data from 101 patients with neuroblastoma
Summary
Neuroblastoma is the most common pediatric malignancy in children, accounting for approximately15% of all cancer-related pediatric deaths [1,2,3]. Many neuroblastoma patients are resistant to chemotherapeutic drugs and develop progressive disease [8,9,10]. For this reason, it is crucial to study the mechanisms of drug resistance and to develop effective treatment regimens for patients with neuroblastoma. Repressor element-1 silencing transcription (REST) factor is a zinc finger transcription factor that modulates a number of genes in neural and non-neural cells [11,12,13] It plays critical roles in neural differentiation [14,15], and its expression decreases quickly in neural stem cells and is maintained at low levels in neurons after differentiation [16]. To the best of our current knowledge, no study has reported any relationship between REST expression and clinical outcome in neuroblastoma
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