A three-gene expression signature model for risk stratification of patients with neuroblastoma Journal Article
| Authors: | Garcia, I.; Mayol, G.; Rios, J.; Domenech, G.; Cheung, N. K. V.; Oberthuer, A.; Fischer, M.; Maris, J. M.; Brodeur, G. M.; Hero, B.; Rodriguez, E.; Suñol, M.; Galván, P.; de Torres, C.; Mora, J.; Lavarino, C. |
| Article Title: | A three-gene expression signature model for risk stratification of patients with neuroblastoma |
| Abstract: | Purpose: 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. Experimental Design: 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. Conclusion: We propose for the first time in neuroblastoma, a technically simple PCR-based predictor model that could help refine current risk stratification systems. ©2012 AACR. |
| Keywords: | adolescent; adult; child; controlled study; event free survival; preschool child; school child; child, preschool; cancer surgery; major clinical study; overall survival; cancer radiotherapy; cancer staging; drug megadose; antineoplastic agent; polymerase chain reaction; gene expression; gene expression profiling; nerve tissue proteins; cohort analysis; genetic association; genetic variability; risk factors; morphology; risk assessment; mathematical model; chromosome aberration; oncogene; gene expression regulation, neoplastic; infant; infant, newborn; neuroblastoma; reverse transcriptase polymerase chain reaction; oligonucleotide array sequence analysis; gene identification; models, genetic; multivariate analysis; dna helicases; predictive value; nm23 nucleoside diphosphate kinases; mathematical analysis; kaplan-meier estimate; microtubule-associated proteins; principal component analysis; chd5 gene; gnb1 gene; nme1 gene; pafah1b1 gene; ptprf gene; rere gene; 1-alkyl-2-acetylglycerophosphocholine esterase |
| Journal Title: | Clinical Cancer Research |
| Volume: | 18 |
| Issue: | 7 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2012-04-01 |
| Start Page: | 2012 |
| End Page: | 2023 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-11-2483 |
| PROVIDER: | scopus |
| PUBMED: | 22328561 |
| PMCID: | PMC4240975 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 May 2012" - "CODEN: CCREF" - "Source: Scopus" |
