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

Abstract

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.

• Authors: Alexander Schramm, Johannes H Schulte, Ludger Klein-Hitpass, Werner Havers, Hauke Sieverts, Bernd Berwanger, Holger Christiansen, Patrick Warnat, Benedikt Brors, Jürgen Eils, Roland Eils, Angelika Eggert
• Journal: Oncogene (Oncogene) Vol. 24 Issue 53 Pg. 7902-12 (Nov 24 2005) ISSN: 0950-9232 [Print] England
• PMID: 16103881 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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