Source
Department of Pediatric Oncology and Hematology, University of Cologne, Cologne, Germany. andre.oberthuer@uk-koeln.de
Abstract
PURPOSE:
To predict individual survival times for neuroblastoma patients from gene expression data using the cancer survival prediction using automatic relevance determination (CASPAR) algorithm.
EXPERIMENTAL DESIGN:
A first set of oligonucleotide microarray gene expression profiles comprising 256 neuroblastoma patients was generated. Then, CASPAR was combined with a leave-one-out cross-validation to predict individual times for both the whole cohort and subgroups of patients with unfavorable markers, including stage 4 disease (n = 67), unfavorable genetic alterations, intermediate-risk or high-risk stratification by the German neuroblastoma trial, and patients predicted as unfavorable by a recently described gene expression classifier (n = 83). Prediction accuracy of individual survival times was assessed by Kaplan-Meier analyses and time-dependent receiver operator characteristics curve analyses. Subsequently, classification results were validated in an independent cohort (n = 120).
RESULTS:
CASPAR separated patients with divergent outcome in both the initial and the validation cohort [initial set, 5y-OS 0.94 +/- 0.04 (predicted long survival) versus 0.38 +/- 0.17 (predicted short survival), P < 0.0001; validation cohort, 5y-OS 0.94 +/- 0.07 (long) versus 0.40 +/- 0.13 (short), P < 0.0001]. Time-dependent receiver operator characteristics analyses showed that CASPAR-predicted individual survival times were highly accurate (initial set, mean area under the curve for first 10 years of overall survival prediction 0.92 +/- 0.04; validation set, 0.81 +/- 0.05). Furthermore, CASPAR significantly discriminated short (<5 years) from long survivors (>5 years) in subgroups of patients with unfavorable markers with the exception of MYCN-amplified patients (initial set). Confirmatory results with high significance were observed in the validation cohort [stage 4 disease (P = 0.0049), NB2004 intermediate-risk or high-risk stratification (P = 0.0017), and unfavorable gene expression prediction (P = 0.0017)].
CONCLUSIONS:
CASPAR accurately forecasts individual survival times for neuroblastoma patients from gene expression data.