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Precision prognostication in neuroblastomas via clinically validated E2F activity signatures.

Donghan Cai1,2, Huihuang Xu1,2, Shiwei He3

  • 1Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China.

Frontiers in Immunology
|July 2, 2025
PubMed
Summary

A new prognostic signature based on E2F-related genes effectively stratifies high-risk neuroblastoma (NB) patients. This signature offers potential biomarkers for improved prognosis and targeted therapy in NB.

Keywords:
E2F-related genesdrug sensitivityimmuneneuroblastomaprognosis

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Area of Science:

  • Pediatric Oncology
  • Molecular Biology
  • Cancer Genomics

Background:

  • Neuroblastoma (NB) is the most common childhood extracranial solid tumor.
  • High-risk NB (HR-NB) has poor survival due to aggressive biology and treatment resistance.
  • The prognostic and therapeutic roles of E2F transcription factors in NB are not well understood.

Purpose of the Study:

  • To identify E2F-associated molecular subtypes in NB.
  • To develop and validate a prognostic signature for NB risk stratification.
  • To explore the relationship between E2F-related subtypes and the tumor immune microenvironment, mutation burden, and drug sensitivity.

Main Methods:

  • Consensus clustering of transcriptomic data from GEO, TARGET, and E-MTAB-8248 cohorts.
  • LASSO regression for constructing and validating a prognostic signature.
  • Analysis of immune infiltration, tumor mutation burden (TMB), and drug sensitivity using CIBERSORT, ESTIMATE, and GDSC databases.

Main Results:

  • Four E2F-related genes (MAD2L1, CDC25A, CKS2, NME1) formed a prognostic nomogram, stratifying patients into high- and low-risk groups.
  • Low-risk patients showed significantly better overall survival (P < 0.05).
  • High-risk group exhibited lower immune/stromal scores, altered immune cell infiltration, distinct mutation spectra, and differential drug sensitivity (P < 0.001).

Conclusions:

  • The E2F-related prognostic signature accurately stratifies NB patients.
  • This signature serves as a potential biomarker for prognosis and targeted therapy in HR-NB.
  • The findings provide insights into NB tumor biology, immune landscape, and therapeutic strategies.