%0 Journal Article %1 Oberthuer2006 %A Oberthuer, André %A Berthold, Frank %A Warnat, Patrick %A Hero, Barbara %A Kahlert, Yvonne %A Spitz, Rüdiger %A Ernestus, Karen %A König, Rainer %A Haas, Stefan %A Eils, Roland %A Schwab, Manfred %A Brors, Benedikt %A Westermann, Frank %A Fischer, Matthias %D 2006 %J J Clin Oncol %K Analysis; Array Assessment; Biological, Disease-Free Expression Gene Germany, Hazards Humans; Japan, Markers, Models; Multivariate Neoplastic; Neuroblastoma, Odds Oligonucleotide Predictive Profiling; Proportional Ratio; Regulation, Reproducibility Results; Risk Sequence States, Survival Survival; Tests; Tumor United Value analysis/genetics; chemistry; epidemiology epidemiology; of %N 31 %P 5070--5078 %R 10.1200/JCO.2006.06.1879 %T Customized oligonucleotide microarray gene expression-based classification of neuroblastoma patients outperforms current clinical risk stratification. %U http://dx.doi.org/10.1200/JCO.2006.06.1879 %V 24 %X To develop a gene expression-based classifier for neuroblastoma patients that reliably predicts courses of the disease.Two hundred fifty-one neuroblastoma specimens were analyzed using a customized oligonucleotide microarray comprising 10,163 probes for transcripts with differential expression in clinical subgroups of the disease. Subsequently, the prediction analysis for microarrays (PAM) was applied to a first set of patients with maximally divergent clinical courses (n = 77). The classification accuracy was estimated by a complete 10-times-repeated 10-fold cross validation, and a 144-gene predictor was constructed from this set. This classifier's predictive power was evaluated in an independent second set (n = 174) by comparing results of the gene expression-based classification with those of risk stratification systems of current trials from Germany, Japan, and the United States.The first set of patients was accurately predicted by PAM (cross-validated accuracy, 99\%). Within the second set, the PAM classifier significantly separated cohorts with distinct courses (3-year event-free survival EFS 0.86 +/- 0.03 favorable; n = 115 v 0.52 +/- 0.07 unfavorable; n = 59 and 3-year overall survival 0.99 +/- 0.01 v 0.84 +/- 0.05; both P < .0001) and separated risk groups of current neuroblastoma trials into subgroups with divergent outcome (NB2004: low-risk 3-year EFS 0.86 +/- 0.04 v 0.25 +/- 0.15, P < .0001; intermediate-risk 1.00 v 0.57 +/- 0.19, P = .018; high-risk 0.81 +/- 0.10 v 0.56 +/- 0.08, P = .06). In a multivariate Cox regression model, the PAM predictor classified patients of the second set more accurately than risk stratification of current trials from Germany, Japan, and the United States (P < .001; hazard ratio, 4.756 95\% CI, 2.544 to 8.893).Integration of gene expression-based class prediction of neuroblastoma patients may improve risk estimation of current neuroblastoma trials.

@article{Oberthuer2006, __markedentry = {[bbrors:6]}, abstract = {To develop a gene expression-based classifier for neuroblastoma patients that reliably predicts courses of the disease.Two hundred fifty-one neuroblastoma specimens were analyzed using a customized oligonucleotide microarray comprising 10,163 probes for transcripts with differential expression in clinical subgroups of the disease. Subsequently, the prediction analysis for microarrays (PAM) was applied to a first set of patients with maximally divergent clinical courses (n = 77). The classification accuracy was estimated by a complete 10-times-repeated 10-fold cross validation, and a 144-gene predictor was constructed from this set. This classifier's predictive power was evaluated in an independent second set (n = 174) by comparing results of the gene expression-based classification with those of risk stratification systems of current trials from Germany, Japan, and the United States.The first set of patients was accurately predicted by PAM (cross-validated accuracy, 99\%). Within the second set, the PAM classifier significantly separated cohorts with distinct courses (3-year event-free survival [EFS] 0.86 +/- 0.03 [favorable; n = 115] v 0.52 +/- 0.07 [unfavorable; n = 59] and 3-year overall survival 0.99 +/- 0.01 v 0.84 +/- 0.05; both P < .0001) and separated risk groups of current neuroblastoma trials into subgroups with divergent outcome (NB2004: low-risk 3-year EFS 0.86 +/- 0.04 v 0.25 +/- 0.15, P < .0001; intermediate-risk 1.00 v 0.57 +/- 0.19, P = .018; high-risk 0.81 +/- 0.10 v 0.56 +/- 0.08, P = .06). In a multivariate Cox regression model, the PAM predictor classified patients of the second set more accurately than risk stratification of current trials from Germany, Japan, and the United States (P < .001; hazard ratio, 4.756 [95\% CI, 2.544 to 8.893]).Integration of gene expression-based class prediction of neuroblastoma patients may improve risk estimation of current neuroblastoma trials.}, added-at = {2015-04-09T12:36:21.000+0200}, author = {Oberthuer, Andr{\'{e}} and Berthold, Frank and Warnat, Patrick and Hero, Barbara and Kahlert, Yvonne and Spitz, R{\"{u}}diger and Ernestus, Karen and K{\"{o}}nig, Rainer and Haas, Stefan and Eils, Roland and Schwab, Manfred and Brors, Benedikt and Westermann, Frank and Fischer, Matthias}, biburl = {https://www.bibsonomy.org/bibtex/229d3b52e41b5f7db4cbcb8362c2f6ea3/bbrors}, doi = {10.1200/JCO.2006.06.1879}, institution = {Children's Hospital, Department of Pediatric Oncology and Hematology, University of Cologne, Kerpener Strasse 62, D-50924 Cologne, Germany. andre.oberthuer@uk-koeln.de}, interhash = {c1f3c7b54c43d092371f53d556fe7c11}, intrahash = {29d3b52e41b5f7db4cbcb8362c2f6ea3}, journal = {J Clin Oncol}, keywords = {Analysis; Array Assessment; Biological, Disease-Free Expression Gene Germany, Hazards Humans; Japan, Markers, Models; Multivariate Neoplastic; Neuroblastoma, Odds Oligonucleotide Predictive Profiling; Proportional Ratio; Regulation, Reproducibility Results; Risk Sequence States, Survival Survival; Tests; Tumor United Value analysis/genetics; chemistry; epidemiology epidemiology; of}, language = {eng}, medline-pst = {ppublish}, month = Nov, number = 31, owner = {bbrors}, pages = {5070--5078}, pii = {24/31/5070}, pmid = {17075126}, timestamp = {2015-04-09T12:36:21.000+0200}, title = {Customized oligonucleotide microarray gene expression-based classification of neuroblastoma patients outperforms current clinical risk stratification.}, url = {http://dx.doi.org/10.1200/JCO.2006.06.1879}, volume = 24, year = 2006 }