Prognostic analysis of E2F transcription factors E2F1 and E2F3 in four independent pediatric neuroblastoma cohorts

Background Previously, we had analyzed the prognosis of E2F transcription factors across adult tumor types. However, the expressions and prognosis of E2F transcription factors in pediatric neuroblastoma have not yet been fully studied. Methods The prognosis of E2F transcription factors was determined in four independent pediatric neuroblastoma cohorts from Therapeutically Applicable Research to Generate Effective Treatments (TARGET), Gene Expression Omnibus (GEO) and European ArrayExpres datasets using Kaplan-Meier and cox regression analysis. Results E2F regulated gene set was associated with the event free survival and the overall survival of neuroblastoma. E2F1 and E2F3 were prognostic factors in all four independent pediatric neuroblastoma cohorts. Over-expressions of E2F1 or E2F3 were correlated with the shorted event free survival and overall survival of neuroblastoma. Expression levels of E2F1 and E2F3 were higher in neuroblastoma patients with MYCN amplification or age at diagnosis >= 18 months. Moreover, the prognostic significance of E2F1 or E2F3 in neuroblastoma was independent of MYCN amplification and age of diagnosis. Combinations of E2F1, E2F3 with MYCN amplification or age of diagnosis achieved better prognosis of neuroblastoma. Identification of 234 genes were associated with E2F1 and E2F3 expressions in neuroblastoma and those genes were significantly enriched in cell cycle signaling pathway. Also, higher scores of cell cycle signaling pathway were correlated with the adverse prognosis of neuroblastoma. Conclusions E2F transcription factors E2F1 and E2F3 were prognostic makers of neuroblastoma.