Integrative analysis of single-cell and bulk RNA sequencing data for discovery of senescent TAMs prognostic characteristics in neuroblastoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41491450", "kind": "science-record", "revision": 3, "content_hash": "sha256:f48d8dcc1d0f401d0f1ec9281c4b026e04bda92340b15ef6ad1d1e55f7107f5b", "created_at": "2026-11-01T20:31:28Z", "updated_at": "2026-11-01T22:15:15Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrative analysis of single-cell and bulk RNA sequencing data for discovery of senescent TAMs prognostic characteristics in neuroblastoma.", "doi": "10.1186/s12885-025-15517-7", "pmid": "41491450", "authors": ["Sitong Qiu", "Youyang Hu", "Yiming Wang", "Hua Xian", "Qiyou Yin"], "journal": "BMC cancer", "year": 2026, "abstract": "BACKGROUND: Tumor-associated macrophages (TAMs) comprise heterogeneous subtypes with context-dependent functions in tumor immunity. Although macrophage senescence influences diverse diseases, its role in neuroblastoma (NB) progression remains undefined.\nMETHODS: Single-cell RNA sequencing (scRNA-seq) data from NB samples (GEO: GSE147766) were analyzed to identify TAM subtypes. Senescence-associated signatures were characterized via pseudotime trajectory, cell-cell communication, and functional assays. A prognostic model was developed using Cox/LASSO regression and validated in independent cohorts (TARGET-NBL, E-MTAB-8248). Drug sensitivity and immune microenvironment differences were compared between risk groups. In vitro validation assessed EIF5's role in TAM senescence and NB progression.\nRESULTS: We identified a senescent TAM subset (C0) exhibits a hybrid M1/M2 state with a dominance of M2-like features. Pseudotime analysis revealed differentiation from non-senescent TAMs (C1), accompanied by upregulated LILRB1, LILRB2, IL10, and CXCL8. A 7-gene prognostic signature (AMD1, ARL4A, BRD2, DDX3X, EIF5, SLC43A2, ZEB2) stratified patients into risk groups with distinct survival (P < 0.001). High-risk patients displayed impaired anti-tumor immunity (reduced CD8⁺ T cells, elevated TIDE scores) and differential drug sensitivity. EIF5 knockdown suppressed senescence markers (p21/p16) in macrophages and inhibited NB cell proliferation/migration.\nCONCLUSIONS: Senescent TAMs influence NB immunosuppression and progression. EIF5 is a key regulator of TAM senescence and a potential therapeutic target. Our risk model may guide clinical stratification and targeted interventions.", "claims": [{"id": "claim-method", "statement": "Subsequently, univariate Cox regression analysis was used to evaluate the prognosis-related MSRGs, and MSRGs with p < 0.001 were selected as candidate variables, and then entered the LASSO regression.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41491450", "locator": "sections[11] \"Construction and validation of senescence-related gene prognostic features\" paragraph 2", "quote": "Subsequently, univariate Cox regression analysis was used to evaluate the prognosis-related MSRGs, and MSRGs with p < 0.001 were selected as candidate variables, and then entered the LASSO regression."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data generated or analyzed during this study are included in this published article and its supplementary information files are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41491450", "locator": "sections[44] \"notes\" paragraph 1", "quote": "Data generated or analyzed during this study are included in this published article and its supplementary information files are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A 7-gene prognostic signature stratified neuroblastoma patients into risk groups with distinct survival.", "kind": "quantitative", "target": {"value": 0.001, "unit": "p-value", "tolerance": null, "source": "A 7-gene prognostic signature (AMD1, ARL4A, BRD2, DDX3X, EIF5, SLC43A2, ZEB2) stratified patients into risk groups with distinct survival (P < 0.001)."}, "evidence": [{"asset": "source:pmid:41491450", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A 7-gene prognostic signature (AMD1, ARL4A, BRD2, DDX3X, EIF5, SLC43A2, ZEB2) stratified patients into risk groups with distinct survival (P < 0.001)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A 7-gene prognostic signature stratified neuroblastoma patients into risk groups with distinct survival.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:41491450"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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