Downregulation of ferroptosis-related Genes can regulate the invasion and migration of osteosarcoma cells.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40399425", "kind": "science-record", "revision": 3, "content_hash": "sha256:8044c9252e36850aed11daf4661fd79b51c4b0e4cf73c03ec903bf9d5ebc78ff", "created_at": "2026-11-01T20:30:32Z", "updated_at": "2026-11-01T22:14:05Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Downregulation of ferroptosis-related Genes can regulate the invasion and migration of osteosarcoma cells.", "doi": "10.1038/s41598-025-02319-x", "pmid": "40399425", "authors": ["Rui Ding", "Le Liao", "Jiahui Chen", "Jian Zhang", "Shenghao Cai", "Xinxin Miao", "Tao Li", "Jiangminghao Zhao", "Qi Chen", "Xigao Cheng", "Jianjian Deng"], "journal": "Scientific reports", "year": 2025, "abstract": "Osteosarcoma (OS) is a prevalent form of bone cancer among younger people, particularly children and adolescents. Ferroptosis is a non-apoptotic cell death identified by increased levels of iron-dependent lipid peroxidation. This study was designed to develop a prognostic model based on differentially expressed genes (DEGs) associated with ferroptosis and examined the functions of ferroptosis-related genes (FRGs) in OS cells. Gene expression profiles in OS were retrieved from TARGET and GEO databases, while GTEx provided data for healthy tissues. Prognostic genes were identified through bioinformatics analysis and data integration. In vitro experiments, cell cultures, qRT-PCR, immunohistochemistry (IHC), cell transfection, Edu assays, DHE assays, migration, and invasion assays validated the prognostic model and explored the functional role of FRGs in OS cells. Univariate Cox regression analysis demonstrated that 12 DEGs were differentially expressed. Based on four FRGs in OS constructed a risk-scoring model. The high-risk (HR) group showed a considerably lower OS rate than the low-risk (LR) group (p < 0.001 in the TARGET and p < 0.05 in the GSE21257 cohorts). A risk score was validated as an independent predictive factor for OS via multivariate Cox regression. Functional analysis shows that these FRGs affect the occurrence of ferroptosis by influencing the intracellular ROS levels and play a regulatory role in the proliferation, migration, and infiltration of OS cells. The findings suggested that four FRGs demonstrate significant prognostic value in OS, offering potential insights into novel therapeutic targets for OS treatment.", "claims": [{"id": "claim-method", "statement": "Uni- and multivariate Cox regression analyses were carried out to predict OS independently.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40399425", "locator": "sections[14] \"Statistical analysis\" paragraph 2", "quote": "Uni- and multivariate Cox regression analyses were carried out to predict OS independently."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data generated or analysed during this study are included in this published article and its supplementary information files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40399425", "locator": "sections[31] \"notes\" paragraph 1", "quote": "All data generated or analysed during this study are included in this published article and its supplementary information files."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The four-FRG risk-scoring model significantly stratified overall survival in osteosarcoma patients in both cohorts.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40399425", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The high-risk (HR) group showed a considerably lower OS rate than the low-risk (LR) group (p < 0.001 in the TARGET and p < 0.05 in the GSE21257 cohorts)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The four-FRG risk-scoring model significantly stratified overall survival in osteosarcoma patients in both cohorts.", "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:40399425"], "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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Further, immunohistochemistry (IHC) was performed to compare protein level", "both OS cells and normal cells (n = 3) (A); Immunohistochemical analysis compared the protein expression lev"], "order_basis": "paper_text_order:748", "id": "assay:1"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["s, qRT-PCR, immunohistochemistry (IHC), cell transfection, Edu assays, DHE assays, migration, and inva", "Materials and methods Cell cultures and transfection MG63, Saos-2, 143B, U2OS, and hFOB 1.19 were", "y genes in SAOS-2 and MG-63 cells, siRNA was transfected into the cells as per the manufacturer’s gui", "from Guangzhou Ruibo Biotechnology Co., Ltd. Transfection of Si-NC and specific siRNAs was performed u"], "order_basis": "paper_text_order:781", "id": "assay:2"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["stitute of Cell Biology in China. Cells were cultured in DMEM (ATCC, USA) with 10% FBS with 1% penici", "ultures and transfection MG63, Saos-2, 143B, U2OS, and hFOB 1.19 were obtained from the Shangh", "he four FRGs were also validated in 143B and U2OS cells (Fig. S1). IHC revealed that in OS tis"], "order_basis": "paper_text_order:1792", "id": "assay:3"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Uni- and multivariate Cox regression analyses were carried out to predict OS independently."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}