Overexpression of TNFSF11 reduces GPX4 levels and increases sensitivity to ferroptosis inducers in lung adenocarcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38594779", "kind": "science-record", "revision": 4, "content_hash": "sha256:220411352605285adeb6e66c94f51e8435b36bc6082c4abe63524284237f2e6a", "created_at": "2026-11-01T19:20:33Z", "updated_at": "2026-11-01T22:54:05Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Overexpression of TNFSF11 reduces GPX4 levels and increases sensitivity to ferroptosis inducers in lung adenocarcinoma.", "doi": "10.1186/s12967-024-05112-y", "pmid": "38594779", "authors": ["Zizhen Li", "Wenhua Lu", "Feng Yin", "Peiting Zeng", "Heping Li", "Amin Huang"], "journal": "Journal of translational medicine", "year": 2024, "abstract": "BACKGROUND: Lung adenocarcinoma (LUAD), the most common and lethal subtype of lung cancer, continues to be a major health concern worldwide. Despite advances in targeted and immune therapies, only a minority of patients derive substantial benefits. As a result, the urgent need for novel therapeutic strategies to improve lung cancer treatment outcomes remains undiminished.\nMETHODS: In our study, we employed the TIMER database to scrutinize TNFSF11 expression across various cancer types. We further examined the differential expression of TNFSF11 in normal and tumor tissues utilizing the TCGA-LUAD dataset and tissue microarray, and probed the associations between TNFSF11 expression and clinicopathological parameters within the TCGA-LUAD dataset. We used the GSE31210 dataset for external validation. To identify genes strongly linked to TNFSF11, we engaged LinkedOmics and conducted a KEGG pathway enrichment analysis using the WEB-based Gene SeT AnaLysis Toolkit. Moreover, we investigated the function of TNFSF11 through gene knockdown or overexpression approaches and explore its function in tumor cells. The therapeutic impact of ferroptosis inducers in tumors overexpressing TNFSF11 were also investigated through in vivo and in vitro experiments. Through these extensive analyses, we shed light on the potential role of TNFSF11 in lung adenocarcinoma, underscoring potential therapeutic targets for this malignancy.\nRESULTS: This research uncovers the overexpression of TNFSF11 in LUAD patients and its inverse correlation with peroxisome-related enzymes. By utilizing gene knockdown or overexpression assays, we found that TNFSF11 was negatively associated with GPX4. Furthermore, cells with TNFSF11 overexpression were relatively more sensitive to the ferroptosis inducers.\nCONCLUSIONS: Our research has provided valuable insights into the role of TNFSF11, revealing its negative regulation of GPX4, which could be influential in crafting therapeutic strategies. These findings set the stage for further exploration into the mechanisms underpinning the relationship between TNFSF11 and GPX4, potentially opening up new avenues for precision medicine in the treatment of LUAD.", "claims": [{"id": "claim-method", "statement": "The construction of survival curves was achieved through the Kaplan-Meier method, with the log-rank test applied for further analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38594779", "locator": "sections[17] \"Statistical analysis\" paragraph 2", "quote": "The construction of survival curves was achieved through the Kaplan-Meier method, with the log-rank test applied for further analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets and materials of this study are derived from the following public databases. NCBI Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/), The Cancer Genome Atlas (TCGA) database (https://portal.gdc.cancer.gov/), TIMER2.0 database (http://timer.comp-genomics.org/), LinkedOmics (http://www.linkedomics.org/login.php). Other data will be obtained from the first author, Amin Huang, upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38594779", "locator": "sections[34] \"Data availability\" paragraph 2", "quote": "The datasets and materials of this study are derived from the following public databases. NCBI Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/), The Cancer Genome Atlas (TCGA) database (https://portal.gdc.cancer.gov/), TIMER2.0 database (http://timer.comp-genomics.org/), LinkedOmics (http://www.linkedomics.org/login.php). Other data will be obtained from the first author, Amin Huang, upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Patients with high TNFSF11 expression had significantly shorter overall survival and progression-free intervals in LUAD.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38594779", "locator": "sections[21] \"High TNFSF11 gene expression predicts an adverse outcome in LUAD\" paragraph 2", "quote": "As illustrated in Fig. 4A-B, Kaplan-Meier analysis indicated that patients with high TNFSF11 expression had significantly shorter overall survival (OS) and progression-free intervals (PFI)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Patients with high TNFSF11 expression had significantly shorter overall survival and progression-free intervals in LUAD.", "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:38594779"], "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:GSE31210"], "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:GSE31210"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38594779", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12967-024-05112-y", "sha256": "sha256:34a08333e7f122eab4eb78e95fb5ceedb901bf25e48b23dec6686c0b330e937d", "bytes": 58077, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12967-024-05112-y", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11005202", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE31210", "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=GSE31210", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE31210", "version": null, "note": "The datasets and materials of this study are derived from the following public databases. 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