RBBP4: A novel diagnostic and prognostic biomarker for non-small-cell lung cancer correlated with autophagic cell death.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39109577", "kind": "science-record", "revision": 3, "content_hash": "sha256:1a5398be7acc434e6a97e0ce527c06e3fefc93a52630645241bb6ef25659674f", "created_at": "2026-11-01T20:29:12Z", "updated_at": "2026-11-01T22:12:24Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "RBBP4: A novel diagnostic and prognostic biomarker for non-small-cell lung cancer correlated with autophagic cell death.", "doi": "10.1002/cam4.70090", "pmid": "39109577", "authors": ["Yajing Zhan", "Zhiqian Zhang", "Ankang Yin", "Xiyang Su", "Nan Tang", "Yi Chen", "Zebin Zhang", "Wei Chen", "Juan Wang", "Wei Wang"], "journal": "Cancer medicine", "year": 2024, "abstract": "BACKGROUND: Non-small-cell lung cancer (NSCLC) often presents at later stages, typically associated with poor prognosis. Autophagy genes play a role in the progression of tumors. This study investigated the clinical relevance, prognostic value, and biological significance of RBBP4 in NSCLC.\nMETHODS: We assessed RBBP4 expression using the GSE30219 and TCGA NSCLC datasets and NSCLC cells, exploring its links with clinical outcomes, tumor immunity, and autophagy genes through bioinformatics analysis after transcriptome sequencing of RBBP4-knockdown and control PC9 cells. We identified differentially expressed genes (DEGs) and conducted Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and protein-protein interaction network analyses. The significance of autophagy-related DEGs was evaluated for diagnosis and prognosis using the GSE30219 dataset. Experiments both in vivo and in vitro explored the biological mechanisms behind RBBP4-mediated autophagic cell death in NSCLC.\nRESULTS: RBBP4 overexpression in NSCLC correlates with a poorer prognosis. Eighteen types of immune cell were significantly enriched in cultures that had low RBBP4 expression compared high expression. DEGs associated with RBBP4 are enriched in autophagy pathways. Transcriptomic profiling of the PC9 cell line identified autophagy-related DEGs associated with RBBP4 that exhibited differential expression in NSCLC, suggesting prognostic applications. In vitro experiments demonstrated that RBBP4 knockdown induced autophagy and apoptosis in PC9 cells, promoting cell death, which was inhibited by 3-MA. In vivo, targeted siRNA against RBBP4 significantly reduced tumor development in PC9 cell-injected nude mice, elevating autophagy-related protein levels and inducing apoptosis and necrosis in tumor tissues.\nCONCLUSION: In NSCLC, RBBP4 upregulation correlates with poor prognosis and altered immunity. Its knockdown induces autophagic cell death in NSCLC cells. These results indicate RBBP4 as a potential NSCLC diagnostic marker and its autophagy modulation as a prospective therapeutic target.", "claims": [{"id": "claim-method", "statement": "Differences in RBBP4 expression were analyzed using the Wilcoxon test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39109577", "locator": "sections[4] \"The association of RBBP4 expression with clinical factors in NSCLC\" paragraph 2", "quote": "Differences in RBBP4 expression were analyzed using the Wilcoxon test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in this study are included in the article itself and/or Supplementary Material. The corresponding authors can be contacted with any reasonable inquiries.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39109577", "locator": "sections[43] \"DATA AVAILABILITY STATEMENT\" paragraph 2", "quote": "The original contributions presented in this study are included in the article itself and/or Supplementary Material. The corresponding authors can be contacted with any reasonable inquiries."}], "state": "complete"}, {"id": "claim-target-result", "statement": "RBBP4 overexpression in NSCLC correlates with a poorer prognosis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39109577", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "RBBP4 overexpression in NSCLC correlates with a poorer prognosis."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "RBBP4 overexpression in NSCLC correlates with a poorer prognosis.", "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:39109577"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE30219"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_wilcoxon", "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:GSE30219"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39109577", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1002/cam4.70090", "sha256": "sha256:8e8d70c2b0c26e48f97cb4018a215d0b68d2a85c818f0153c5b6cc7a109aee98", "bytes": 70952, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1002/cam4.70090", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11304277", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE30219", "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=GSE30219", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE30219", "version": null, "note": "The original contributions presented in this study are included in the article itself and/or Supplementary Material. The corresponding authors can be contacted with any reasonable inquiries.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in this study are included in the article itself and/or Supplementary Material. 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We identified differe", "In vitro experiments demonstrated that RBBP4 knockdown induced autophagy and apoptosis in PC9 cells", "ith poor prognosis and altered immunity. Its knockdown induces autophagic cell death in NSCLC cells", "ich was inhibited by 3-MA. In vivo, targeted siRNA against RBBP4 significantly reduced tumor de"], "order_basis": "paper_text_order:618", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["using the GSE30219 dataset. Experiments both in vivo and in vitro explored the biological mechani", "ing cell death, which was inhibited by 3-MA. 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Positive apoptotic nuclei appeared brown or"], "order_basis": "paper_text_order:1610", "id": "assay:3"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["from both groups (magnification, 200×). (F) Immunohistochemistry was employed to determine the protein levels", "graft tumor model. 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