Evaluation of genes identified by microarray analysis in favorable neuroblastoma

Abstract

The biological heterogeneity of neuroblastoma results in a varied outcome ranging from spontaneous regression to fatal tumor progression. Microarray expression profiling and genetic polymorphism arrays may help identify key genes that differ in aggressive neuroblastomas from those observed in tumors associated with a favorable outcome. Total RNA was extracted from 16 neuroblastomas obtained from patients who subsequently died of the disease and from 16 favorable neuroblastomas and analyzed using a human whole genome oligomicroarray (55K CodeLink). Genes overexpressed in favorable tumors were subsequently analyzed in 121 neuroblastoma tumors obtained before chemotherapy using real-time RT-PCR. And among these cases, expression levels of these genes were also analyzed in 20 tumors obtained after chemotherapy. Oligomicroarray analysis revealed the overexpression of 283 genes in favorable tumors that were associated with either regressing or maturing tumors. Three candidate genes, including DHRS3, NROB1, and CYP26A1, were selected that were significantly overexpressed in favorable tumors by quantitative real-time RT-PCR (P < 0.01). No cases with overexpression of all three genes showed poor outcomes. In 20 post-chemotherapeutic tumors, the expression levels of these genes increased in the cases where patients survived but decreased in the fatal cases. Using microarray expression profiling, we identified genes that exhibit altered gene expression in neuroblastoma tumors associated with a favorable outcome. These candidates warrant further study for use in risk assessment and/or as therapeutic targets in neuroblastoma.