Ten-gene signature reveals the significance of clinical prognosis and immuno-correlation of osteosarcoma and study on novel skeleton inhibitors regarding MMP9.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34261456", "kind": "science-record", "revision": 4, "content_hash": "sha256:5e2bd5688d08905eae635265b28c972ece221b38ce73e6938ea6f08e606d4092", "created_at": "2026-11-01T15:41:43Z", "updated_at": "2026-11-01T22:04:13Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Ten-gene signature reveals the significance of clinical prognosis and immuno-correlation of osteosarcoma and study on novel skeleton inhibitors regarding MMP9.", "doi": "10.1186/s12935-021-02041-4", "pmid": "34261456", "authors": ["Weihang Li", "Ziyi Ding", "Dong Wang", "Chengfei Li", "Yikai Pan", "Yingjing Zhao", "Hongzhe Zhao", "Tianxing Lu", "Rui Xu", "Shilei Zhang", "Bin Yuan", "Yunlong Zhao", "Yanjiang Yin", "Yuan Gao", "Jing Li", "Ming Yan"], "journal": "Cancer cell international", "year": 2021, "abstract": "OBJECTIVES: This study aimed to identify novel targets in the carcinogenesis, therapy and prognosis of osteosarcoma from genomic level, together with screening ideal lead compounds with potential inhibition regarding MMP-9.\nMETHODS: Gene expression profiles from GSE12865, GSE14359, GSE33382, GSE36001 and GSE99671 were obtained respectively from GEO database. Differentially expressed genes were identified, and functional enrichment analysis, such as GO, KEGG, GSEA, PPI were performed to make a comprehensive understanding of the hub genes. Next, a series of high-precision computational techniques were conducted to screen potential lead compounds targeting MMP9, including virtual screening, ADME, toxicity prediction, and accurate docking analysis.\nRESULTS: 10 genes, MMP9, CD74, SPP1, CXCL12, TYROBP, FCER1G, HCLS1, ARHGDIB, LAPTM5 and IGF1R were identified as hub genes in the initiation of osteosarcoma. Machine learning, multivariate Cox analysis, ssGSEA and survival analysis demonstrated that these genes had values in prognosis, immune-correlation and targeted treatment. Tow novel compounds, ZINC000072131515 and ZINC000004228235, were screened as potential inhibitor regarding MMP9, and they could bind to MMP9 with favorable interaction energy and high binding affinity. Meanwhile, they were precited to be efficient and safe drugs with low-ames mutagenicity, none weight evidence of carcinogenicity, as well as non-toxic with liver.\nCONCLUSIONS: This study revealed the significance of 10-gene signature in the development of osteosarcoma. Besides, drug candidates identified in this study provided a solid basis on MMP9 inhibitors' development.", "claims": [{"id": "claim-method", "statement": "The independent prognostic ability of the gene signature was evaluated by univariate and multivariate Cox analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34261456", "locator": "sections[13] \"Prediction of overall survival in clinical application\" paragraph 2", "quote": "The independent prognostic ability of the gene signature was evaluated by univariate and multivariate Cox analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data used and analyzed in this study are available upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34261456", "locator": "sections[48] \"notes\" paragraph 1", "quote": "The data used and analyzed in this study are available upon reasonable request."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:34261456"], "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:GSE12865"], "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:GSE12865"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34261456", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12935-021-02041-4", "sha256": "sha256:8e7a15a4470d5bfa652314fd047e950e4a77b4adf1c3c2d8f3897349c22f7f27", "bytes": 76900, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12935-021-02041-4", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8281696", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE12865", "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=GSE12865", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE12865", "version": null, "note": "The data used and analyzed in this study are available upon reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data used and analyzed in this study are available upon reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM288005", "GSM288006", "GSM322691", "GSM322692", "GSM322693", "GSM322694", "GSM322695", "GSM322696", "GSM322697", "GSM322698", "GSM322699", "GSM322700", "GSM322701", "GSM322702"], "sample_count": 14, "group_sizes": null, "group_sizes_basis": null, "platform": "6244", "taxon": "Homo sapiens", "title": "Gene expression of human paediatric osteosarcoma tumour samples relative to normal human osteoblasts", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE14359", "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=GSE14359", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE14359", "version": null, "note": "The data used and analyzed in this study are available upon reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data used and analyzed in this study are available upon reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM359137", "GSM359138", "GSM359139", "GSM359140", "GSM359141", "GSM359142", "GSM359143", "GSM359144", "GSM359145", "GSM359146", "GSM359147", "GSM359148", "GSM359149", "GSM359150", "GSM359151", "GSM359152", "GSM359153", "GSM359154", "GSM359155", "GSM359156"], "sample_count": 20, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "Expression data from conventional osteosarcoma compared to primary non-neoplastic osteoblast cells", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE33382", "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=GSE33382", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE33382", "version": null, "note": "The data used and analyzed in this study are available upon reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data used and analyzed in this study are available upon reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM825623", "GSM825624", "GSM825625", "GSM825626", "GSM825627", "GSM825628", "GSM825629", "GSM825630", "GSM825631", "GSM825632", "GSM825633", "GSM825634", "GSM825635", "GSM825636", "GSM825637", "GSM825638", "GSM825639", "GSM825640", "GSM825641", "GSM825642", "GSM825643", "GSM825644", "GSM825645", "GSM825646", "GSM825647", "GSM825648", "GSM825649", "GSM825650", "GSM825651", "GSM825652", "GSM825653", "GSM825654", "GSM825655", "GSM825656", "GSM825657", "GSM825658", "GSM825659", "GSM825660", "GSM825661", "GSM825662", "GSM825663", "GSM825664", "GSM825665", "GSM825666", "GSM825667", "GSM825668", "GSM825669", "GSM825670", "GSM825671", "GSM825672", "GSM825673", "GSM825674", "GSM825675", "GSM825676", "GSM825677", "GSM825678", "GSM825679", "GSM825680", "GSM825681", "GSM825682", "GSM825683", "GSM825684", "GSM825685", "GSM825686", "GSM825687", "GSM825688", "GSM825689", "GSM825690", "GSM825691", "GSM825692", "GSM825693", "GSM825694", "GSM825695", "GSM825696", "GSM825697", "GSM825698", "GSM825699", "GSM825700", "GSM825701", "GSM825702", "GSM825703", "GSM825704", "GSM825705", "GSM825706", "GSM825707", "GSM825708", "GSM825709"], "sample_count": 87, "group_sizes": null, "group_sizes_basis": null, "platform": "10295", "taxon": "Homo sapiens", "title": "Genome-wide gene expression analysis of high-grade osteosarcoma", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE36001", "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=GSE36001", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE36001", "version": null, "note": "The data used and analyzed in this study are available upon reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data used and analyzed in this study are available upon reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM879156", "GSM879157", "GSM879158", "GSM879159", "GSM879160", "GSM879161", "GSM879162", "GSM879163", "GSM879164", "GSM879165", "GSM879166", "GSM879167", "GSM879168", "GSM879169", "GSM879170", "GSM879171", "GSM879172", "GSM879173", "GSM879174", "GSM879175", "GSM879176", "GSM879177", "GSM879178", "GSM879179", "GSM879180"], "sample_count": 25, "group_sizes": null, "group_sizes_basis": null, "platform": "6102", "taxon": "Homo sapiens", "title": "Integrative analysis reveals relationships of genetic and epigenetic alterations in osteosarcoma [gene expression]", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE99671", "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=GSE99671", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE99671", "version": null, "note": "The data used and analyzed in this study are available upon reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data used and analyzed in this study are available upon reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2649696", "GSM2649697", "GSM2649698", "GSM2649699", "GSM2649700", "GSM2649701", "GSM2649702", "GSM2649703", "GSM2649704", "GSM2649705", "GSM2649706", "GSM2649707", "GSM2649708", "GSM2649709", "GSM2649710", "GSM2649711", "GSM2649712", "GSM2649713", "GSM2649714", "GSM2649715", "GSM2649716", "GSM2649717", "GSM2649718", "GSM2649719", "GSM2649720", "GSM2649721", "GSM2649722", "GSM2649723", "GSM2649724", "GSM2649725", "GSM2649726", "GSM2649727", "GSM2649728", "GSM2649729", "GSM2649730", "GSM2649731", "GSM2652426", "GSM2652427", "GSM2652428", "GSM2652429", "GSM2652430", "GSM2652431", "GSM2652432", "GSM2652433", "GSM2652434", "GSM2652435", "GSM2652436", "GSM2652437", "GSM2652438", "GSM2652439", "GSM2652440"], "sample_count": 51, "group_sizes": null, "group_sizes_basis": null, "platform": "20148", "taxon": "Homo sapiens", "title": "Whole transcriptome analysis identifies differentially regulated networks between osteosarcoma and normal bone samples", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE12865 not downloaded", "asset:data:geo:GSE12865 licence not read", "asset:data:geo:GSE14359 not downloaded", "asset:data:geo:GSE14359 licence not read", "asset:data:geo:GSE33382 not downloaded", "asset:data:geo:GSE33382 licence not read", "asset:data:geo:GSE36001 not downloaded", "asset:data:geo:GSE36001 licence not read", "asset:data:geo:GSE99671 not downloaded", "asset:data:geo:GSE99671 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "PPI"}}, {"id": "method-2", "family": null, "specific": null, "label": "Multivariate Cox analysis", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The independent prognostic ability of the gene signature was evaluated by univariate and multivariate Cox analysis."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: ppi_network."}, "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": ["GSE12865", "GSE14359", "GSE33382", "GSE36001", "GSE99671"], "resolved_accessions": ["GSE12865", "GSE14359", "GSE33382", "GSE36001", "GSE99671"], "statements": ["The data used and analyzed in this study are available upon reasonable request."], "basis": "The paper names GSE12865, GSE14359, GSE33382, GSE36001, GSE99671 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "assets": ["source:pmid:34261456", "data:geo:GSE12865"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE12865"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:32:23Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 52124, "completion_tokens": 3300, "cached_tokens": 784}}, "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:34261456", "type": "paper", "label": "pmid:34261456"}, {"id": "source:pmid:34261456", "type": "manuscript", "label": "PMID 34261456 full text"}, {"id": "data:geo:GSE12865", "type": "dataset", "label": "GEO GSE12865"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34261456", "type": "paper", "label": "pmid:34261456"}, {"id": "source:pmid:34261456", "type": "manuscript", "label": "PMID 34261456 full text"}, {"id": "data:geo:GSE12865", "type": "dataset", "label": "GEO GSE12865"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34261456", "type": "extraction", "used": ["source:pmid:34261456"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE12865", "type": "accession_resolution", "used": ["data:geo:GSE12865"], "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:34261456", "parent_hash": "sha256:1116bbcdb087eab3b07f8ce80f56aa1e8bf3b90103d04e3a80efb3dfc38bd680", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE12865 licence not read", "asset:data:geo:GSE12865 not downloaded", "asset:data:geo:GSE14359 licence not read", "asset:data:geo:GSE14359 not downloaded", "asset:data:geo:GSE33382 licence not read", "asset:data:geo:GSE33382 not downloaded", "asset:data:geo:GSE36001 licence not read", "asset:data:geo:GSE36001 not downloaded", "asset:data:geo:GSE99671 licence not read", "asset:data:geo:GSE99671 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "network_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["PPI"], "order_basis": "analysis_only", "id": "assay:1"}]}