A three-gene expression signature model for risk stratification of patients with neuroblastoma.
OBJECTIVE
Neuroblastoma is an embryonal tumor with contrasting clinical courses. Despite elaborate stratification strategies, precise clinical risk assessment still remains a challenge. The purpose of this study was to develop a PCR-based predictor model to improve clinical risk assessment of patients with neuroblastoma.


METHODS
The model was developed using real-time PCR gene expression data from 96 samples and tested on separate expression data sets obtained from real-time PCR and microarray studies comprising 362 patients.


RESULTS
On the basis of our prior study of differentially expressed genes in favorable and unfavorable neuroblastoma subgroups, we identified three genes, CHD5, PAFAH1B1, and NME1, strongly associated with patient outcome. The expression pattern of these genes was used to develop a PCR-based single-score predictor model. The model discriminated patients into two groups with significantly different clinical outcome [set 1: 5-year overall survival (OS): 0.93 ± 0.03 vs. 0.53 ± 0.06, 5-year event-free survival (EFS): 0.85 ± 0.04 vs. 0.042 ± 0.06, both P < 0.001; set 2 OS: 0.97 ± 0.02 vs. 0.61 ± 0.1, P = 0.005, EFS: 0.91 ± 0.8 vs. 0.56 ± 0.1, P = 0.005; and set 3 OS: 0.99 ± 0.01 vs. 0.56 ± 0.06, EFS: 0.96 ± 0.02 vs. 0.43 ± 0.05, both P < 0.001]. Multivariate analysis showed that the model was an independent marker for survival (P < 0.001, for all). In comparison with accepted risk stratification systems, the model robustly classified patients in the total cohort and in different clinically relevant risk subgroups.


CONCLUSIONS
We propose for the first time in neuroblastoma, a technically simple PCR-based predictor model that could help refine current risk stratification systems.
Developmental Tumor Biology Laboratory, Hospital Sant Joan de Deu, Edificio Docente 4th Floor, 08950 Esplugues de Llobregat, Barcelona 08950, Spain.
Idoia
I
Garcia
Gemma
G
Mayol
José
J
Ríos
Gema
G
Domenech
Nai-Kong V
NK
Cheung
André
A
Oberthuer
Matthias
M
Fischer
John M
JM
Maris
Garrett M
GM
Brodeur
Barbara
B
Hero
Eva
E
Rodríguez
Mariona
M
Suñol
Patricia
P
Galvan
Carmen
C
de Torres
Jaume
J
Mora
Cinzia
C
Lavarino
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics; D002675:Child, Preschool; D004265:DNA Helicases / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008957:Models, Genetic; D015999:Multivariate Analysis; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors
D008869:Microtubule-Associated Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009419:Nerve Tissue Proteins; C517938:NME1 protein, human; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human; D004265:DNA Helicases; C471926:CHD5 protein, human