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题目:: Transcription profiling of human neuroblastoma cells with and without MYCN oncogene induction and doxorubicin treatment
ID:
状态:: 发布时间June 1, 2007 , 更新时间 May 1, 2014 , 提交时间 March 7, 2007,
物种:: Homo sapiens
摘要:: Purpose: Clinical courses of neuroblastomas (NBs) range from rapid progression with fatal outcome despite intensive multimodality therapies to spontaneous regression. Amplified MYCN oncogene defines a subgroup with poor outcome. However, a substantial number of MYCN single-copy NBs exhibits an aggressive phenotype similar to that of MYCN-amplified NBs even in the absence of high MYCN mRNA and/or protein levels. Experimental Design: To identify shared molecular mechanisms that mediate the aggressive phenotype in MYCN amplified and single-copy high-risk NBs, we defined genetic programs evoked by ectopically expressed MYCN in vitro and analyzed them in high-risk versus low-risk NB tumors (n=49) using cDNA microarrays. Candidate gene and protein expression was validated in a separate cohort of 117 patients using quantitative PCR (QPCR) and in a panel of NB tumors using immunohistochemistry. Results: We identified a genetic signature characterized by Skp2, encoding the F-box protein of the SCFSkp2 E3-ligase, and a subset of MYCN and of E2F targets to be highly expressed in high-risk NBs. We validated the findings for Skp2 and analyzed its expression in relation to MYCN and E2F-1 expression in a separate cohort (n=117) using QPCR. Most importantly, high Skp2 expression proved to be a highly significant marker of dire prognosis independent of both MYCN status and disease stage, on the basis of multivariate analysis of event-free survival (hazard ratio, 3.54
实验种类:: transcription profiling by array
样本量:: 30
实验设计:
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数据号:: E-CVDE-3
数据状态:: 无法自动分析，您可以尝试手动分析数据。

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