Identification of potential gene signatures associated with osteosarcoma by integrated bioinformatics analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34123594", "kind": "science-record", "revision": 7, "content_hash": "sha256:7e8e15e5aa1ad6c45d459b7a5740d65de6b42208a1f021b629b5937e2e69fb4e", "created_at": "2026-11-01T15:41:38Z", "updated_at": "2026-11-01T22:03:57Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of potential gene signatures associated with osteosarcoma by integrated bioinformatics analysis.", "doi": "10.7717/peerj.11496", "pmid": "34123594", "authors": ["Yutao Jia", "Yang Liu", "Zhihua Han", "Rong Tian"], "journal": "PeerJ", "year": 2021, "abstract": "BACKGROUND: Osteosarcoma (OS) is the most primary malignant bone cancer in children and adolescents with a high mortality rate. This work aims to screen novel potential gene signatures associated with OS by integrated microarray analysis of the Gene Expression Omnibus (GEO) database.\nMATERIAL AND METHODS: The OS microarray datasets were searched and downloaded from GEO database to identify differentially expressed genes (DEGs) between OS and normal samples. Afterwards, the functional enrichment analysis, protein-protein interaction (PPI) network analysis and transcription factor (TF)-target gene regulatory network were applied to uncover the biological function of DEGs. Finally, two published OS datasets (GSE39262 and GSE126209) were obtained from GEO database for evaluating the expression level and diagnostic values of key genes.\nRESULTS: In total 1,059 DEGs (569 up-regulated DEGs and 490 down-regulated DEGs) between OS and normal samples were screened. Functional analysis showed that these DEGs were markedly enriched in 214 GO terms and 54 KEGG pathways such as pathways in cancer. Five genes (CAMP, METTL7A, TCN1, LTF and CXCL12) acted as hub genes in PPI network. Besides, METTL7A, CYP4F3, TCN1, LTF and NETO2 were key genes in TF-gene network. Moreover, Pax-6 regulated four key genes (TCN1, CYP4F3, NETO2 and CXCL12). The expression levels of four genes (METTL7A, TCN1, CXCL12 and NETO2) in GSE39262 set were consistent with our integration analysis. The expression levels of two genes (CXCL12 and NETO2) in GSE126209 set were consistent with our integration analysis. ROC analysis of GSE39262 set revealed that CYP4F3, CXCL12, METTL7A, TCN1 and NETO2 had good diagnostic values for OS patients. ROC analysis of GSE126209 set revealed that CXCL12, METTL7A, TCN1 and NETO2 had good diagnostic values for OS patients.", "claims": [{"id": "claim-method", "statement": "Subsequently, MetaMA (https://cran.r-project.org/web/packages/metaMA/), an R package, was used to combine data from four GEO datasets.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34123594", "locator": "sections[4] \"Data pre-processing and DEGs identification\" paragraph 2", "quote": "Subsequently, MetaMA (https://cran.r-project.org/web/packages/metaMA/), an R package, was used to combine data from four GEO datasets."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The following information was supplied regarding data availability:The data is available at NCBI GEO: GSE12865, GSE19276, GSE87624, GSE99671, GSE39262, and GSE126209.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34123594", "locator": "sections[21] \"Data Availability\" paragraph 2", "quote": "The following information was supplied regarding data availability:The data is available at NCBI GEO: GSE12865, GSE19276, GSE87624, GSE99671, GSE39262, and GSE126209."}], "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:34123594"], "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:34123594", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.11496", "sha256": 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GSE99671, GSE39262, and GSE126209.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The following information was supplied regarding data availability:The data is available at NCBI GEO: GSE12865, GSE19276, GSE87624, GSE99671, GSE39262, and GSE126209.", "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:GSE19276", 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["LAPTM4B", "1.499", "1.78E−08", "2.21E−06", "Up-regulation"], ["ZC3H8", "1.563", "1.97E−08", "2.41E−06", "Up-regulation"], ["SLC35F2", "1.570", "3.46E−08", "3.90E−06", "Up-regulation"], ["IRX2", "1.534", "5.03E−08", "5.19E−06", "Up-regulation"], ["ZNF593", "1.404", "7.11E−08", "6.78E−06", "Up-regulation"], ["FLAD1", "1.451", "7.54E−08", "7.10E−06", "Up-regulation"], ["KCNG1", "1.456", "1.32E−07", "1.16E−05", "Up-regulation"], ["FGD1", "1.304", "2.59E−07", "2.04E−05", "Up-regulation"], ["RPAP2", "1.480", "2.63E−07", "2.06E−05", "Up-regulation"], ["DYRK4", "1.405", "2.83E−07", "2.20E−05", "Up-regulation"], ["EDARADD", "1.360", "3.06E−07", "2.33E−05", "Up-regulation"], ["PDCD5", "1.285", "3.77E−07", "2.80E−05", "Up-regulation"], ["TMEM97", "1.349", "4.04E−07", "2.95E−05", "Up-regulation"], ["GNL2", "1.311", "4.14E−07", "3.01E−05", "Up-regulation"], ["HOXB6", "1.527", "4.47E−07", "3.17E−05", "Up-regulation"], ["ZZZ3", "1.504", "5.79E−07", "3.99E−05", "Up-regulation"], ["CAMP", "−4.158", "0", "0", "Down-regulation"], ["AHSP", "−3.156", "0", "0", "Down-regulation"], ["OLFM4", "−3.108", "0", "0", "Down-regulation"], ["LTF", "−3.006", "0", "0", "Down-regulation"], ["ADH1C", "−2.814", "0", "0", "Down-regulation"], ["CXCL12", "−2.746", "0", "0", "Down-regulation"], ["BPI", "−2.556", "0", "0", "Down-regulation"], ["HBD", "−2.615", "8.88E−16", "5.32E−13", "Down-regulation"], ["TCN1", "−2.522", "1.11E−15", "6.40E−13", "Down-regulation"], ["FABP4", "−2.296", "7.77E−15", "4.31E−12", "Down-regulation"], ["RAB37", "−2.279", "2.02E−14", "1.08E−11", "Down-regulation"], ["FCN1", "−2.320", "2.95E−14", "1.53E−11", "Down-regulation"], ["TMEM154", "−2.279", "3.13E−14", "1.55E−11", "Down-regulation"], ["METTL7A", "−2.181", "5.44E−14", "2.47E−11", "Down-regulation"], ["CYP4F3", "−2.304", "6.66E−14", "2.94E−11", "Down-regulation"], ["CAT", "−2.109", "3.44E−13", "1.43E−10", "Down-regulation"], ["CHL1", "−1.974", "5.51E−13", "2.17E−10", "Down-regulation"], ["TMEM132C", "−1.860", "5.19E−12", "1.85E−09", "Down-regulation"], ["SERPINB2", "−3.082", "5.64E−12", "1.97E−09", "Down-regulation"], ["SLC28A3", "−2.118", "8.26E−12", "2.69E−09", "Down-regulation"]], "row_count": 41, "column_count": 5, "numeric_cells": 130, "header_rows": 1, "locator": "section[10]/table-wrap[1]#table-1"}}, {"id": "asset:table:pmid:34123594:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:530ff1dd5ceafeb25ec5573210cbad15fd20bfb0c686851d59d8bff1de9c7d54", "bytes": 3885, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#table-2", "version": null, "note": "The top 20 significantly enriched KEGG pathways.", "structure": {"pmcid": "PMC8164836", "section_index": 11, "section_title": "GO and KEGG enrichment analysis of DEGs", "row_count": 21, "column_count": 5}, "table": {"label": "Table 2", "caption": "The top 20 significantly enriched KEGG pathways.", "rows": [["ID", "Term", "P_value", "Count", "Gene Symbols"], ["hsa04923", "Regulation of lipolysis in adipocytes", "0.0001", "10", "ADRB2, FABP4, PDE3B, PIK3CD, PLIN1, PTGER3, IRS2, ABHD5, PNPLA2, ADCY4"], ["hsa04141", "Protein processing in endoplasmic reticulum", "0.0001", "19", "BAG1, EIF2S1, HSPA2, LMAN1, MAN1A1, MAP3K5, P4HB, EIF2AK2, RPN2, RRBP1, SSR2, PREB, SEC24A, SEC61G, UBQLN2, DNAJB11, UBQLN4, DNAJC1, UBE2J2"], ["hsa05200", "Pathways in cancer", "0.0002", "34", "BCL2L1, CASP8, CDKN2A, CEBPA, CKS1B, COL4A1, DVL1, E2F1, EPAS1, FGF7, FGF13, FLT3, MTOR, GLI2, GLI3, GNAQ, PIK3CD, PTEN, PTGER2, PTGER3, RARB, RXRA, CXCL12, SKP2, STAT5A, TGFB3, TGFBR2, VEGFA, NCOA4, FGF16, PIAS2, ARHGEF11, LEF1, ADCY4, SHC1, CALM1, CHEK1, ELK1, FDPS, GPS2, MSX2, RANBP1, TLN1, VCAM1, TLN2"], ["hsa01230", "Biosynthesis of amino acids", "0.0004", "11", "CTH, ENO1, GAPDH, PC, SHMT1, TALDO1, TKT, TPI1, SDS, RPIA, AADAT, CAT, MDH2, ME1, MCEE"], ["hsa04974", "Protein digestion and absorption", "0.0019", "11", "COL2A1, COL4A1, COL5A2, COL10A1, COL11A1, COL17A1, CPA3, SLC7A8, COL18A1, COL27A1, SLC16A10"], ["hsa04722", "Neurotrophin signaling pathway", "0.0022", "13", "CALM1, MAPK14, MAP3K5, NFKBIE, NTF3, NTRK2, PIK3CD, PRKCD, RPS6KA2, SHC1, MAGED1, PRDM4, IRAK3"], ["hsa04152", "AMPK signaling pathway", "0.0023", "13", "CPT1A, ELAVL1, MTOR, LEP, PIK3CD, PPP2R5A, PPP2R5D, PRKAB2, IRS2, CREB5, CAMKK2, STRADB, CREB3L1, PRKCD, PRKCE, PTEN, RPS6KA2, TBC1D4, JAK2, NFKBIE, RXRA, SOCS2, CAT, ADCY4, CALM1, ELK1, FLOT2, PDE3B, PRKAR2B, SHC1, INPP5K, HSPA2"], ["M00007", "Pentose phosphate pathway, non-oxidative phase, fructose 6P =>ribose 5P", "0.0026", "3", "TALDO1, TKT, RPIA"], ["hsa03060", "Protein export", "0.0028", "5", "OXA1L, SRP54, SRP72, SEC61G, SRPRB"], ["hsa04933", "AGE-RAGE signaling pathway in diabetic complications", "0.0041", "11", "COL4A1, MAPK14, JAK2, PIK3CD, PRKCD, PRKCE, STAT5A, TGFB3, TGFBR2, VCAM1, VEGFA, CD247, MTOR, NFKBIE, RXRA, STAT6, IL27RA, LHB, SHC1, SOCS2, 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"format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:0fc6031ce801f02a51ab922ac9d0fa897dd04d46a4b99bc203ec21990eceaff3", "bytes": 1153, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#table-3", "version": null, "note": "The top 6 TF that has the most downstream genes.", "structure": {"pmcid": "PMC8164836", "section_index": 13, "section_title": "TF-target network analysis", "row_count": 7, "column_count": 3}, "table": {"label": "Table 3", "caption": "The top 6 TF that has the most downstream genes.", "rows": [["TF", "Number∗", "Gene Symbol"], ["Pax-4", "31", "FLAD1, ZZZ3, GNL2, EDARADD, RTKN, LTF, CAMP, CHL1, ADH1C, TMEM154, IRX2, FABP4, LAPTM4B, SLC28A3, FGD1, CXCL12, HBD, TCN1, CAT, SLC35F2, DYRK4, METTL7A, OLFM4, AHSP, RAB37, TMEM97, SERPINB2, CYP4F3, PDCD5, BPI, KCNG1"], ["1-Oct", "22", "FLAD1, GNL2, RPAP2, EDARADD, ZC3H8, CHL1, CAMP, IRX2, FABP4, TMEM65, SLC28A3, HBD, TCN1, CAT, TMEM132C, DYRK4, METTL7A, TMEM97, HOXB6, SERPINB2, BPI, KCNG1"], ["Nkx2-5", "19", "FLAD1, MLLT11, RPAP2, EDARADD, CAMP, CHL1, TMEM154, LAPTM4B, TMEM65, SLC28A3, FGD1, TCN1, SLC35F2, DYRK4, AHSP, SERPINB2, CYP4F3, KCNG1, BPI"], ["HNF-4", "16", "ZZZ3, ZNF593, GNL2, LTF, CHL1, CAMP, LAPTM4B, SLC28A3, FGD1, CXCL12, HBD, SLC35F2, METTL7A, RAB37, CYP4F3, KCNG1"], ["FOXD3", "14", "GNL2, RPAP2, EDARADD, ZC3H8, CHL1, LTF, FABP4, FGD1, HBD, DYRK4, METTL7A, OLFM4, NETO2, RAB37"], ["Pax-6", "13", "EDARADD, GNL2, CHL1, TMEM65, SLC28A3, CXCL12, HBD, TCN1, DYRK4, NETO2, SERPINB2, CYP4F3, KCNG1"]], "row_count": 7, "column_count": 3, "numeric_cells": 17, "header_rows": 1, "locator": "section[13]/table-wrap[1]#table-3"}}], "gaps": ["asset:data:geo:GSE12865 not downloaded", "asset:data:geo:GSE12865 licence not read", "asset:data:geo:GSE19276 not downloaded", "asset:data:geo:GSE19276 licence not read", "asset:data:geo:GSE39262 not downloaded", "asset:data:geo:GSE39262 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