Abstract
BackgroundMYCN amplification and age are two critical prognostic factors of pediatric neuroblastoma. Previously, we had revealed the prognosis of MYCN target genes. However, the prognostic effects of age related genes in neuroblastoma are unclear.MethodsThe prognostic significance of age and MYCN amplification was determined through multivariate cox regression and Kaplan-Meier survival analysis. Genes differentially expressed in MYCN non-amplified younger neuroblastoma patients were identified using Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) datasets. The prognostic effects of age related genes ALCAM, CACNA2D3, DST, EPB41L4A and KIF1B in pediatric neuroblastoma patients were determined by Kaplan-Meier survival.ResultsIn a pediatric pan-cancer analysis, age was associated with the overall survival of pediatric B-lineage acute lymphoblastic leukemia, neuroblastoma and wilms tumor in TARGET dataset. Moreover, the prognostic effects of age in neuroblastoma were validated using two independent neuroblastoma cohorts. Furthermore, age and MYCN amplification were independent prognostic factors in pediatric neuroblastoma. Compared with MYCN non-amplified older neuroblastoma patients, MYCN non-amplified younger neuroblastoma patients had better clinical outcomes. ALCAM, CACNA2D3, DST, EPB41L4A and KIF1B were highly expressed in MYCN non-amplified younger neuroblastoma patients. And the higher expression levels of ALCAM, CACNA2D3, DST, EPB41L4A or KIF1B were associated with better prognosis of MYCN non-amplified neuroblastoma patients. DST was an independent prognostic factor in MYCN non-amplified neuroblastoma patients and MYCN non-amplified neuroblastoma younger patients with higher DST expression levels had the best clinical overall survival.ConclusionsAge related gene DST was an independent prognostic factor in MYCN non-amplified neuroblastoma. MYCN non-amplified younger neuroblastoma patients with higher DST expression levels had the best clinical overall survival.
Highlights
MYCN amplification and age are two critical prognostic factors of pediatric neuroblastoma
Age is associated with the overall survival of pediatric neuroblastoma patients Previously, we revealed the prognostic effects of age in each adult tumor type using The Cancer Genome Atlas (TCGA) datasets [24]
Similar to the results derived from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset, we found that, compared with younger pediatric neuroblastoma, older pediatric neuroblastoma patients had worse clinical outcomes in both GSE49710 and GSE85047 datasets (Fig. 2a)
Summary
MYCN amplification and age are two critical prognostic factors of pediatric neuroblastoma. We had revealed the prognosis of MYCN target genes. MYCN amplification is an important prognostic factor in neuroblastoma [3]. Pediatric neuroblastoma patients with MYCN amplification are associated with poor prognosis [4,5,6]. MYCN belongs to the MYC transcription factor family and regulates the expression levels of multiple target genes [7]. Independent of MYCN amplification, MYCN expression levels [8] and MYCN regulated signature [9] are correlated with the unfavorable outcomes of neuroblastoma. Using published gene expression datasets, previously, we had identified six MYCN target genes which could be used to predict the clinical outcomes of neuroblastoma [10]. Bromodomain inhibitors have specific efficacy in MYCN amplified neuroblastoma [11,12,13]
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