ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1612667
This article is part of the Research TopicAdvancements in Immune Heterogeneity in Inflammatory Diseases and Cancer: New Targets, Mechanisms, and StrategiesView all 16 articles
Precision Prognostication in Neuroblastomas via Clinically Validated E2F Activity Signatures
Provisionally accepted
- 1Fujian Provincial Hospital, Fuzhou, China
- 2Fujian Medical University, Fuzhou, Fujian Province, China
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Background Neuroblastoma (NB) is the most common extracranial solid tumor in children, with high-risk NB (HR-NB) exhibiting dismal survival rates due to aggressive biology and therapy resistance. E2F transcription factors (E2Fs) are pivotal regulators of cell cycle progression and immune modulation, yet their prognostic and therapeutic implications in NB remain underexplored. Methods Using transcriptomic data from the GEO, TARGET, and E-MTAB-8248 cohorts, we identified E2F-associated molecular subtypes via consensus clustering. A prognostic signature was constructed via LASSO regression and validated for risk stratification. Immune infiltration, tumor mutation burden (TMB), and drug sensitivity were analyzed via the CIBERSORT, ESTIMATE, and GDSC databases.Results Four E2F-related genes (MAD2L1, CDC25A, CKS2, and NME1) were used to construct a prognostic nomogram that stratified patients into high-and low-risk groups, with low-risk patients exhibiting superior overall survival (P < 0.05).Multivariate Cox regression confirmed that the model was an independent prognostic factor (P < 0.001). High-risk patients presented lower immune and stromal scores, reduced immune checkpoint expression, distinct immune cell infiltration patterns, and significant differences in mutation spectrum and drug sensitivity (P < 0.001).The E2F-related prognostic signature effectively stratifies NB patients by risk and provides potential biomarkers for prognosis and targeted therapy in HR-NB patients. The identified signature enhances patient stratification and provides insights into NB tumor biology, the immune landscape, and potential treatment strategies.
Keywords: Neuroblastoma, E2F-related genes, Prognosis, Immune, Drug sensitivity Abbreviation Neuroblastoma, NB, high-risk NB, HR-NB, Tumor mutation burden, TMB, tumor immune microenvironment, TIME, differential expression genes, DEGs, Kaplan -Meier, KM, gene set enrichment analysis, GSEA, simple nucleotide variation, SNV
Received: 16 Apr 2025; Accepted: 29 May 2025.
Copyright: © 2025 Cai, Xu, He, Xu and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Donghan Cai, Fujian Provincial Hospital, Fuzhou, China
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