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Buchumschlag von Accurate prediction of neuroblastoma outcome based on miRNA expression profiles
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Accurate prediction of neuroblastoma outcome based on miRNA expression profiles

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Zeitschriftentitel: International Journal of Cancer
Personen und Körperschaften: Schulte, Johannes H., Schowe, Benjamin, Mestdagh, Pieter, Kaderali, Lars, Kalaghatgi, Prabhav, Schlierf, Stefanie, Vermeulen, Joelle, Brockmeyer, Bent, Pajtler, Kristian, Thor, Theresa, de Preter, Katleen, Speleman, Frank, Morik, Katharina, Eggert, Angelika, Vandesompele, Jo, Schramm, Alexander
In: International Journal of Cancer, 127, 2010, 10, S. 2374-2385
Medientyp: E-Article
Sprache: Englisch
veröffentlicht:
Wiley
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Zusammenfassung: <jats:title>Abstract</jats:title><jats:p>For neuroblastoma, the most common extracranial tumour of childhood, identification of new biomarkers and potential therapeutic targets is mandatory to improve risk stratification and survival rates. MicroRNAs are deregulated in most cancers, including neuroblastoma. In this study, we analysed 430 miRNAs in 69 neuroblastomas by stem‐loop RT‐qPCR. Prediction of event‐free survival (EFS) with support vector machines (SVM) and actual survival times with Cox regression‐based models (CASPAR) were highly accurate and were independently validated. SVM‐accuracy for prediction of EFS was 88.7% (95% CI: 88.5–88.8%). For CASPAR‐based predictions, 5y‐EFS probability was 0.19% (95% CI: 0–38%) in the CASPAR‐predicted short survival group compared with 0.78% (95%CI: 64–93%) in the CASPAR‐predicted long survival group. Both classifiers were validated on an independent test set yielding accuracies of 94.74% (SVM) and 5y‐EFS probabilities as 0.25 (95% CI: 0.0–0.55) for short <jats:italic>versus</jats:italic> 1 ± 0.0 for long survival (CASPAR), respectively. Amplification of the <jats:italic>MYCN</jats:italic> oncogene was highly correlated with deregulation of miRNA expression. In addition, 37 miRNAs correlated with TrkA expression, a marker of excellent outcome, and 6 miRNAs further analysed <jats:italic>in vitro</jats:italic> were regulated upon TrkA transfection, suggesting a functional relationship. Expression of the most significant TrkA‐correlated miRNA, miR‐542‐5p, also discriminated between local and metastatic disease and was inversely correlated with <jats:italic>MYCN</jats:italic> amplification and event‐free survival. We conclude that neuroblastoma patient outcome prediction using miRNA expression is feasible and effective. Studies testing miRNA‐based predictors in comparison to and in combination with mRNA and aCGH information should be initiated. Specific miRNAs (<jats:italic>e.g</jats:italic>., miR‐542‐5p) might be important in neuroblastoma tumour biology, and qualify as potential therapeutic targets.</jats:p>
Umfang: 2374-2385
ISSN: 0020-7136
1097-0215
DOI: 10.1002/ijc.25436