Schulte/Schowe/2010a: Accurate Prediction of Neuroblastoma Outcome based on miRNA Expression Profiles

Bibtype Article
Bibkey Schulte/Schowe/2010a
Author Johannes H. Schulte and Benjamin Schowe and Pieter Mestdagh and Lars Kaderali and Prabhav Kalaghatgi and Stefanie Schlierf and Joelle Vermeulen and Bent Brockmeyer and Kristian Pajtler and Theresa Thor and Katleen de Preter and Frank Speleman and Katharina Morik and Angelika Eggert and Jo Vandesompele and Alexander Schramm
Ls8autor Morik, Katharina
Schowe, Benjamin
Title Accurate Prediction of Neuroblastoma Outcome based on miRNA Expression Profiles
Journal International Journal of Cancer
Abstract 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. We here 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 to 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 vs 1?0.0 for long survival (CASPAR), respectively. Amplification of the MYCN 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 in vitro 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 MYCN 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 (e.g. miR-542-5p) might be important in neuroblastoma tumour biology, and qualify as potential therapeutic targets.
Year 2010
Projekt SFB876-C1
Url http://dx.doi.org/10.1002/ijc.25436
MicroArray Analysis

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