Prediction of clinical outcome and biological characterization of neuroblastoma by expression profiling

Oncogene. 2005 Nov 24;24(53):7902-12. doi: 10.1038/sj.onc.1208936.


Neuroblastoma is a common childhood tumor comprising cases with rapid disease progression as well as spontaneous regression. Although numerous prognostic factors have been identified, risk evaluation in individual patients remains difficult. To define a reliable prognostic predictor and gene signatures characteristic of biological subgroups, we performed mRNA expression profiling of 68 neuroblastomas of all stages. Expression data were analysed using support vector machines (SVM-rbf), prediction analysis of microarrays (PAM), k-nearest neighbors (k-NN) algorithms and multiple decision trees. SVM-rbf performed best of all methods, and predicted recurrence of neuroblastoma with an accuracy of 85% (sensitivity 77%, specificity 94%). PAM identified a classifier of 39 genes reliably predicting outcome with an accuracy of 80%. In comparison, conventional risk stratification based on stage, age and MYCN-status only reached a predictive accuracy of 64%. Kaplan-Meier analysis using the PAM classifier indicated a 5-year survival of 20 versus 78% for patients with unfavorably versus favorably predicted neuroblastomas, respectively (P = 0.0001). Significance analysis of microarrays (SAM) identified additional genes differentially expressed among subgroups. MYCN-amplification and high expression of NTRK1/TrkA demonstrated a strong association with specific gene expression patterns. Our data suggest that microarray-derived data in addition to traditional clinical factors will be useful for risk assessment and defining biological properties of neuroblastoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Cohort Studies
  • Decision Trees
  • Gene Amplification
  • Gene Expression Profiling*
  • Humans
  • Infant
  • Infant, Newborn
  • N-Myc Proto-Oncogene Protein
  • Neoplasm Staging
  • Neuroblastoma / genetics*
  • Neuroblastoma / pathology*
  • Nuclear Proteins / genetics*
  • Oligonucleotide Array Sequence Analysis*
  • Oncogene Proteins / genetics*
  • Prognosis
  • RNA, Messenger / analysis
  • Receptor, trkA / genetics*
  • Risk Assessment
  • Survival Analysis


  • MYCN protein, human
  • N-Myc Proto-Oncogene Protein
  • Nuclear Proteins
  • Oncogene Proteins
  • RNA, Messenger
  • Receptor, trkA