An age-based, RNA expression paradigm for survival biomarker identification for pediatric neuroblastoma and acute lymphoblastic leukemia

Abstract

Abstract Background Pediatric cancer survival rates overall have been improving, but neuroblastoma (NBL) and acute lymphoblastic leukemia (ALL), two of the more prevalent pediatric cancers, remain particularly challenging. One issue not yet fully addressed is distinctions attributable to age of diagnosis. Methods In this report, we verified a survival difference based on diagnostic age for both pediatric NBL and pediatric ALL datasets, with younger patients surviving longer for both diseases. We identified several gene expression markers that correlated with age, along a continuum, and then used a series of age-independent survival metrics to filter these initial correlations. Results For pediatric NBL, we identified 2 genes that are expressed at a higher level in lower surviving patients with an older diagnostic age; and 4 genes that are expressed at a higher level in longer surviving patients with a younger diagnostic age. For pediatric ALL, we identified 3 genes expressed at a higher level in lower surviving patients with an older diagnostic age; and 17 genes expressed at a higher level in longer surviving patients with a younger diagnostic age. Conclusions This process implicated pan-chromosome effects for chromosomes 11 and 17 in NBL; and for the X chromosome in ALL.

Keywords

• Diagnostic age
• Pediatric cancer
• Neuroblastoma
• Acute lymphoblastic leukemia
• Chromosome 17
• Age of onset