DNA Damage Response Genes in Osteosarcoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35251167", "kind": "science-record", "revision": 3, "content_hash": "sha256:2631681ba3649a3510934f0cd9f94400ec802d859ae1d29c1a76b33ab65161a8", "created_at": "2026-11-01T17:37:00Z", "updated_at": "2026-11-01T21:27:22Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "DNA Damage Response Genes in Osteosarcoma.", "doi": "10.1155/2021/9365953", "pmid": "35251167", "authors": ["Ying Tang", "Yan-Xia Liu", "Xiuning Huang", "Peng Li"], "journal": "Journal of oncology", "year": 2021, "abstract": "BACKGROUND: Improving the osteosarcoma (OS) patients' survival has long been a challenge, even though the disease's treatment is on the verge of progress. DNA damage response (DDR) has traditionally been associated with carcinogenesis, tumor growth, and genomic instability. No study has used DDR genes as a signature to identify the prognosis of OS. The goal of this work was to find an effective possible DDR gene biomarker for predicting OS prognosis, which may be useful in clinical diagnosis and therapy.\nMETHODS: To assess gene methylation, univariate and multivariate cox regression analyses were performed on data from OS patients. The data were retrieved from public databases, including the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and the Gene Expression Omnibus (GEO).\nRESULTS: The DDR gene signature was chosen, which included seven genes (NHEJ1, RMI2, SWI5, ERCC2, CLK2, POLG, and MLH1). In the TARGET dataset, patients were categorized into two groups: high-risk and low-risk. Patients with a high-risk score revealed a shorter OS rate (hazard ratio (HR): 3.15, 95% confidence interval (CI): 1.38-4.34, P < 0.001) in comparison with the patients with a low-risk score in the TARGET as a training group. The validation of the prognostic signature accuracy was carried out in relapse and validation cohorts (TARGET, n = 75; GSE21257, n = 53). The signature was found to be an independent predictive factor for OS in multivariate cox regression analysis, and a nomogram model was developed to predict an individual's risk of OS. DDR gene signature involved in Fanconi anemia pathway, nonhomologous end-joining pathway, mismatch repair, and nucleotide excision repair pathway.\nCONCLUSIONS: Our study suggests that the identified novel DDR genes could be a powerful prognostic tool for prognosis evaluation and a valuable tool in predicting the risk factors in OS patients.", "claims": [{"id": "claim-method", "statement": "Being the independent variables, the survival statue and survival time were initially conducted using univariate cox proportional hazards regression analysis of the 276 genes.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35251167", "locator": "sections[9] \"3.1. Evaluation of the Prognostic DDR Genes from the Training Cohort\" paragraph 2", "quote": "Being the independent variables, the survival statue and survival time were initially conducted using univariate cox proportional hazards regression analysis of the 276 genes."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All the data used to support the findings of this study are included within the article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35251167", "locator": "sections[17] \"Data Availability\" paragraph 2", "quote": "All the data used to support the findings of this study are included within the article."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A seven-gene DDR signature stratified osteosarcoma patients by prognosis, with the high-risk group having a shorter overall survival rate than the low-risk group.", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "Patients with a high-risk score revealed a shorter OS rate (hazard ratio (HR): 3.15, 95% confidence interval (CI): 1.38–4.34, P < 0.001) in comparison with the patients with a low-risk score in the TARGET as a training group."}, "evidence": [{"asset": "source:pmid:35251167", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Patients with a high-risk score revealed a shorter OS rate (hazard ratio (HR): 3.15, 95% confidence interval (CI): 1.38–4.34, P < 0.001) in comparison with the patients with a low-risk score in the TARGET as a training group."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A seven-gene DDR signature stratified osteosarcoma patients by prognosis, with the high-risk group having a shorter overall survival rate than the low-risk group.", "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:35251167"], "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:GSE21257"], "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:GSE21257"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35251167", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2021/9365953", "sha256": "sha256:c9da55cf3e0ec6e7592488ad1ebfaa95919f6f8c6c5477e2caafc666ed34461e", "bytes": 19488, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1155/2021/9365953", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8894034", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE21257", "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=GSE21257", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE21257", "version": null, "note": "All the data used to support the findings of this study are included within the article.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All the data used to support the findings of this study are included within the article.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM530667", "GSM530899", "GSM531283", "GSM531284", "GSM531285", "GSM531286", "GSM531287", "GSM531288", "GSM531289", "GSM531290", "GSM531291", "GSM531292", "GSM531293", "GSM531294", "GSM531295", "GSM531296", "GSM531297", "GSM531298", "GSM531299", "GSM531300", "GSM531301", "GSM531302", "GSM531303", "GSM531304", "GSM531305", "GSM531306", "GSM531307", "GSM531308", "GSM531309", "GSM531310", "GSM531311", "GSM531312", "GSM531313", "GSM531314", "GSM531319", "GSM531320", "GSM531321", "GSM531322", "GSM531323", "GSM531324", "GSM531325", "GSM531326", "GSM531327", "GSM531328", "GSM531329", "GSM531330", "GSM531331", "GSM531332", "GSM531333", "GSM531334", "GSM531335", "GSM531351", "GSM531352"], "sample_count": 53, "group_sizes": null, "group_sizes_basis": null, "platform": "10295", "taxon": "Homo sapiens", "title": "Genome-wide gene expression profiling on pre-chemotherapy biopsies of osteosarcoma patients who developed metastases within 5yrs (n=34) and patients who did not develop metastases within 5yrs (n=19)", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE21257 not downloaded", "asset:data:geo:GSE21257 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Being the independent variables, the survival statue and survival time were initially conducted using univariate cox proportional hazards regression analysis of the 276 genes."}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "cox_ph", "expected_value": 95.0, "unit": "per cent", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none."}, {"id": "target-published-estimate-p-value", "claim_id": "claim-target-result", "operation": "cox_ph", "expected_value": 0.001, "unit": "p-value", "tolerance": null, "state": "complete", "note": "The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold."}], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["cox_ph"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE21257"], "resolved_accessions": ["GSE21257"], "statements": ["All the data used to support the findings of this study are included within the article."], "basis": "The paper names GSE21257 in GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:35251167", "data:geo:GSE21257"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE21257"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:36:42Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 6599, "completion_tokens": 1083, "cached_tokens": 128}}, "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:35251167", "type": "paper", "label": "pmid:35251167"}, {"id": "source:pmid:35251167", "type": "manuscript", "label": "PMID 35251167 full text"}, {"id": "data:geo:GSE21257", "type": "dataset", "label": "GEO GSE21257"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35251167", "type": "paper", "label": "pmid:35251167"}, {"id": "source:pmid:35251167", "type": "manuscript", "label": "PMID 35251167 full text"}, {"id": "data:geo:GSE21257", "type": "dataset", "label": "GEO GSE21257"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35251167", "type": "extraction", "used": ["source:pmid:35251167"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE21257", "type": "accession_resolution", "used": ["data:geo:GSE21257"], "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:35251167", "parent_hash": "sha256:c77fa5be12f8492a06b266f4ada2015d74696917563dfde3552e345a0932e2fc", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE21257 licence not read", "asset:data:geo:GSE21257 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["osteosarcoma patients as well as level three RNA-Seq data. As a validation set, the GEO dataset G"], "order_basis": "paper_text_order:2229", "id": "assay:1"}, {"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": ["Being the independent variables, the survival statue and survival time were initially conducted using univariate cox proportional hazards regression analysis of the 276 genes."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}