microRNA signature and expression of Dicer and Drosha can predict prognosis and delineate risk groups in neuroblastoma.

microRNA signature and expression of Dicer and Drosha can predict prognosis and delineate risk groups in neuroblastoma.

Cancer Res. 2010 Aug 30;

Authors: Lin RJ, Lin YC, Chen J, Kuo HH, Chen YY, Diccianni MB, London WB, Chang CH, Yu AL

Neuroblastoma (NB) is a common childhood tumor and accounts for 15% of pediatric cancer deaths. To investigate the microRNA (miRNA) profile and role of Dicer and Drosha in NB, we have assessed the expression of 162 human miRNAs, Dicer and Drosha in 66 NB tumors by using real-time PCR methods. We found global downregulation of miRNA expression in advanced NB and identified 27 miRNAs that can clearly distinguish low- from high-risk patients. Furthermore, expression levels of Dicer or Drosha were low in high risk NB tumors, which accounted for global downregulation of miRNAs in advanced disease and correlated with poor outcome. Notably, for patients with MYCN non-amplified tumors, low expression of Dicer can serve as a significant and independent predictor of poor outcome (HR=9.6, p=0.045, n=52). Using Plausible Neural Networks (PNN) to select a combination of 15 biomarkers which consist of 12 miRNAs signature, expression levels of Dicer and Drosha and age at diagnosis, we were able to segregate all patients into 4 distinct patterns which were highly predictive of clinical outcome. In vitro studies also showed that knockdown of either Dicer or Drosha promoted the growth of NB cell lines. Our results reveal that a combination of 15 biomarkers that can delineate risk groups of NB and serve as a powerful predictor of clinical outcome. Moreover, our findings of growth promotion by silencing Dicer/Drosha implied their potential use as therapeutic targets for neuroblastoma.

PMID: 20805302 [PubMed - as supplied by publisher]

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Posted 2 Sep 2010 6:47 AM by pubmed: neuroblastoma
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There is nothing quite as devastating as hearing that word - neuroblastoma. In seconds your world is turned upside down and your normal life is but a distant memory. You are thrust into a confusing world full of fear. Your child has cancer.

We know. We have been there. The Neuroblastoma Foundation is here for you.

Welcome to our website. It is a place for you to find answers and ask questions. One of the primary goals of the Neuroblastoma Foundation is to ensure that parents, patients and health care professionals find the information they need to make the best treatment decisions possible for children and adults affected by neuroblastoma. There is a vast amount of information throughout the internet, much of which is encapsulated in medical jargon that is so complex that even many medical professionals have difficulty in interpreting its meaning. We are here to help to decipher this information and to make sure you (and your oncologist) understand exactly what it means to you. From treatment decisions to side effects we have parents and experts that have experienced it all and are willing to distill it for you.