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Int J Mol Sci. 2014 Jun 25;15(7):11220-33. doi: 10.3390/ijms150711220.

The REST gene signature predicts drug sensitivity in neuroblastoma cell lines and is significantly associated with neuroblastoma tumor stage.

Author information

1
Department of Neurosurgery, China-Japan Friendship Hospital, Beijing 100029, China. liangjianfengharvard@gmail.com.
2
Department of Bioinformatics and Computational Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. ptong1@mdanderson.org.
3
Department of General Surgery, Jinan Central Hospital, Jinan 250013, China. zhaowanni2000@gmail.com.
4
Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. yaqiao_li@hms.harvard.edu.
5
Department of Neurosurgery, China-Japan Friendship Hospital, Beijing 100029, China. zhangliallan@gmail.com.
6
The Vivan L. Smith Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, TX 77030, USA. ying.xia@uth.tmc.edu.
7
Department of Neurosurgery, China-Japan Friendship Hospital, Beijing 100029, China. yuyanbing2014@gmail.com.

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.

PMID:
24968265
PMCID:
PMC4139778
DOI:
10.3390/ijms150711220
[Indexed for MEDLINE]
Free PMC Article

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