A three-gene expression signature model for risk stratification of patients with neuroblastoma
Menée initialement sur 96 échantillons tumoraux prélevés sur des patients atteints d'un neuroblastome, puis validée sur 362 patients, cette étude identifie trois gènes dont l'expression est associée à la survie des patients
Background: 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 neuroblastoma patients. 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: Based on 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<0.001 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.
Clinical Cancer Research , résumé, 2012