miRNA expression profiling enables risk stratification in archived and fresh neuroblastoma tumor samples.

Abstract

PURPOSE:

More accurate assessment of prognosis is important to further improve the choice of risk-related therapy in neuroblastoma (NB) patients. In this study, we aimed to establish and validate a prognostic miRNA signature for children with NB and tested it in both fresh frozen and archived formalin-fixed paraffin-embedded (FFPE) samples.

EXPERIMENTAL DESIGN:

Four hundred-thirty human mature miRNAs were profiled in two patient subgroups with maximally divergent clinical courses. Univariate logistic regression analysis was used to select miRNAs correlating with NB patient survival. A 25-miRNA gene signature was built using 51 training samples, tested on 179 test samples, and validated on an independent set of 304 fresh frozen tumor samples and 75 archived FFPE samples.

RESULTS:

The 25-miRNA signature significantly discriminates the test patients with respect to progression-free and overall survival (P < 0.0001), both in the overall population and in the cohort of high-risk patients. Multivariate analysis indicates that the miRNA signature is an independent predictor of patient survival after controlling for current risk factors. The results were confirmed in an external validation set. In contrast to a previously published mRNA classifier, the 25-miRNA signature was found to be predictive for patient survival in a set of 75 FFPE neuroblastoma samples.

CONCLUSIONS:

In this study, we present the largest NB miRNA expression study so far, including more than 500 NB patients. We established and validated a robust miRNA classifier, able to identify a cohort of high-risk NB patients at greater risk for adverse outcome using both fresh frozen and archived material.

• Authors: Katleen De Preter, Pieter Mestdagh, Joëlle Vermeulen, Fjoralba Zeka, Arlene Naranjo, Isabella Bray, Victoria Castel, Caifu Chen, Elzbieta Drozynska, Angelika Eggert, Michael D Hogarty, Ewa Izycka-Swieszewska, Wendy B London, Rosa Noguera, Marta Piqueras, Kenneth Bryan, Benjamin Schowe, Peter van Sluis, Jan J Molenaar, Alexander Schramm, Johannes H Schulte, Raymond L Stallings, Rogier Versteeg, Geneviève Laureys, Nadine Van Roy, Frank Speleman, Jo Vandesompele
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 17 Issue 24 Pg. 7684-92 (Dec 15 2011) ISSN: 1557-3265 [Electronic] United States
• PMID: 22031095 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2011 AACR.

Chemical References

• MicroRNAs

Topics

• Case-Control Studies
• Child
• Child, Preschool
• Cohort Studies
• Follow-Up Studies
• Gene Expression Profiling (methods)
• Humans
• Infant
• Kaplan-Meier Estimate
• Logistic Models
• MicroRNAs (genetics)
• Multivariate Analysis
• Neuroblastoma (diagnosis, genetics, therapy)
• Prognosis
• Reproducibility of Results
• Reverse Transcriptase Polymerase Chain Reaction
• Risk Assessment
• Risk Factors
• Time Factors