Precision prognostication in neuroblastomas via clinically validated E2F activity signatures.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40599792", "kind": "science-record", "revision": 3, "content_hash": "sha256:842d3553ff1d5bbbaba9ce118599c1a5b3dde241f16e744c4bcc9fe0b86c5a06", "created_at": "2026-11-01T20:30:41Z", "updated_at": "2026-11-01T22:14:17Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Precision prognostication in neuroblastomas via clinically validated E2F activity signatures.", "doi": "10.3389/fimmu.2025.1612667", "pmid": "40599792", "authors": ["Donghan Cai", "Huihuang Xu", "Shiwei He", "Di Xu", "Lizhi Li"], "journal": "Frontiers in immunology", "year": 2025, "abstract": "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.\nMethods: 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.\nResults: 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).\nConclusions: 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.", "claims": [{"id": "claim-method", "statement": "Kaplan–Meier analysis with a log-rank test was used to compare overall survival between different subgroups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40599792", "locator": "sections[12] \"Statistical methods\" paragraph 2", "quote": "Kaplan–Meier analysis with a log-rank test was used to compare overall survival between different subgroups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40599792", "locator": "sections[24] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/ Supplementary Material . 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This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:E-MTAB-8248"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:E-MTAB-8248"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40599792", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2025.1612667", "sha256": "sha256:95b18b36d7844c8942daf6d7e8a15d584ddcbcb61292889c826ed258c888e49b", "bytes": 53032, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2025.1612667", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12209246", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:E-MTAB-8248", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=E-MTAB-8248", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "E-MTAB-8248", "version": null, "note": "The original contributions presented in the study are included in the article/ Supplementary Material . 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["logrank_test"], "assets": ["source:pmid:40599792", "data:geo:E-MTAB-8248"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:E-MTAB-8248"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:55:52Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 14831, "completion_tokens": 2455, "cached_tokens": 264}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:40599792", "type": "paper", "label": "pmid:40599792"}, {"id": "source:pmid:40599792", "type": "manuscript", "label": "PMID 40599792 full text"}, {"id": "data:geo:E-MTAB-8248", "type": "dataset", "label": "GEO E-MTAB-8248"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40599792", "type": "paper", "label": "pmid:40599792"}, {"id": "source:pmid:40599792", "type": "manuscript", "label": "PMID 40599792 full text"}, {"id": "data:geo:E-MTAB-8248", "type": "dataset", "label": "GEO E-MTAB-8248"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40599792", "type": "extraction", "used": ["source:pmid:40599792"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-E-MTAB-8248", "type": "accession_resolution", "used": ["data:geo:E-MTAB-8248"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:40599792", "parent_hash": "sha256:453aebb3df1608d7ddd2d546cca0a37c5a377193ff070912c84f21a70f23dc53", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:E-MTAB-8248 licence not read", "asset:data:geo:E-MTAB-8248 not downloaded", "asset:data:geo:GSE49711 licence not read", "asset:data:geo:GSE49711 not downloaded", "asset:data:geo:GSE73511 licence not read", "asset:data:geo:GSE73511 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["logrank_test"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Kaplan–Meier analysis with a log-rank test was used to compare overall survival between different subgroups."], "order_basis": "analysis_only", "id": "assay:1"}]}