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59-gene expression signature predicted poor neuroblastoma outcomes

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Researchers have created a gene expression signature that identified patients with neuroblastoma who are at increased risk for poor outcomes.

The researchers used data mining to search through seven published microarray gene-expression studies that included nearly 690 patients with the disease. From that data, they compiled a list of 59 genes to create a prognostic multigene signature using 15 high-risk and 15 low-risk patients who died after a long PFS time.

The gene signature was then tested on 313 test samples and validated in a blind study of 236 tumors.

The researchers found that the signature predicted a five-year PFS of 81.2% (95% CI, 76.8%-87.0%) and a five-year OS of 98% (95% CI, 96.1%-100%) for patients at low molecular risk. For patients at high risk, the signature predicted a five-year PFS of 43.6% (95% CI, 32.4%-58.6%) and a five-year OS of 55% (95% CI, 43.1%-70.1%).

Based on ROC-curve analysis, the probability that the signature would correctly classify a patient was 85.4% (95% CI, 77.7%-93.2%) for OS and 66.9% (95% CI, 59.2%-74.6%) for PFS. The researchers said that was superior to current risk factors such as age, International Neuroblastoma Staging System stage and MYCN status.

The signature had an overall sensitivity of 84.4% (95% CI, 66.5%-94.1%) and a specificity of 86.5% (95% CI, 81.1%-90.6%). Multivariate logistic regression showed that only the signature and INSS stage were independent predictors of OS and PFS.

In the validation study, the signature was independently and statistically significant in a model adjusted for: age, INSS stage, ploidy, MYCN status, grade of differentiation and mitosis karyorrhexis index.

Vermeulen J. Lancet Oncology. 2009;doi:10.1016/S1470-2045(09)70154-8.