Screening of Biomarkers Associated with Osteoarthritis Aging Genes and Immune Correlation Studies.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38268862", "kind": "science-record", "revision": 3, "content_hash": "sha256:3b8490e58e556765ba40c200c6ed5da1dd78790d57d6345180ffac5a0fa4d6fe", "created_at": "2026-11-01T19:20:11Z", "updated_at": "2026-11-01T22:11:06Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Screening of Biomarkers Associated with Osteoarthritis Aging Genes and Immune Correlation Studies.", "doi": "10.2147/IJGM.S447035", "pmid": "38268862", "authors": ["Lanwei Xu", "Zheng Wang", "Gang Wang"], "journal": "International journal of general medicine", "year": 2024, "abstract": "Purpose: Osteoarthritis (OA) is a joint disease with a long and slow course, which is one of the major causes of disability in middle and old-aged people. This study was dedicated to excavating the cellular senescence-associated biomarkers of OA.\nMethods: The Gene Expression Omnibus (GEO) database was searched and five datasets pertaining to OA were obtained. After removing the batch effect, the GSE55235, GSE55457, GSE82107, and GSE12021 datasets were integrated together for screening of the candidate genes by differential analysis and weighted gene co-expression network analysis (WGCNA). Next, those genes were further filtered by machine learning algorithms to obtain cellular senescence-associated biomarkers of OA. Subsequently, enrichment analyses based on those biomarkers were conducted, and we profiled the infiltration levels of 22 types immune cells with the ERSORT algorithm. A lncRNA-miRNA-mRNA regulatory and drug-gene network were constructed. Finally, we validated the senescence-associated biomarkers at both in vivo and in vitro levels.\nResults: Five genes (BCL6, MCL1, SLC16A7, PIM1, and EPHA3) were authenticated as cellular senescence-associated biomarkers in OA. ROC curves demonstrated the reliable capacity of the five genes as a whole to discriminate OA samples from normal samples. The nomogram diagnostic model based on 5 genes proved to be a reliable predictor of OA. Single-gene GSEA results pointed to the involvement of the five biomarkers in immune-related pathways and oxidative phosphorylation in the development of OA. Immune infiltration analysis manifested that the five genes were significantly correlated with differential immune cells. Subsequently, a lncRNA-miRNA-mRNA network and gene-drug network containing were generated based on five cellular senescence-associated biomarkers in OA.\nConclusion: A foundation for understanding the pathophysiology of OA and new insights into OA diagnosis and treatment were provided by the identification of five genes, namely BCL6, MCL1, SLC16A7, PIM1, and EPHA3, as biomarkers associated with cellular senescence in OA.", "claims": [{"id": "claim-method", "statement": "The receiver operating characteristic (ROC) curves were generated using the “pROC” software (version 1.17.0.1).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38268862", "locator": "sections[20] \"Statistical Analysis\" paragraph 2", "quote": "The receiver operating characteristic (ROC) curves were generated using the “pROC” software (version 1.17.0.1)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used in this investigation are available in internet sources. Below, you can find the names of the repository/repositories together with their corresponding accession number(s). The provided URL leads to the National Centre for Biotechnology Information (NCBI) website, GSE55235, GSE55457, GSE82107, GSE12021, and GSE51588. Cellular senescence-related genes (CSRGs) can be download from CellAge database: https://genomics.senescence.info/cells/query.php. The original images of the cell experiments in the article can be accessed at the following link: 10.6084/m9.figshare.24328570", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38268862", "locator": "sections[34] \"Data Available Statement\" paragraph 2", "quote": "The datasets used in this investigation are available in internet sources. Below, you can find the names of the repository/repositories together with their corresponding accession number(s). The provided URL leads to the National Centre for Biotechnology Information (NCBI) website, GSE55235, GSE55457, GSE82107, GSE12021, and GSE51588. Cellular senescence-related genes (CSRGs) can be download from CellAge database: https://genomics.senescence.info/cells/query.php. The original images of the cell experiments in the article can be accessed at the following link: 10.6084/m9.figshare.24328570"}], "state": "complete"}, {"id": "claim-target-result", "statement": "Five cellular senescence-associated biomarkers, BCL6, MCL1, SLC16A7, PIM1, and EPHA3, were identified and combined in a reliable nomogram-based diagnostic model for osteoarthritis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38268862", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Five genes (BCL6, MCL1, SLC16A7, PIM1, and EPHA3) were authenticated as cellular senescence-associated biomarkers in OA."}, {"asset": "source:pmid:38268862", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The nomogram diagnostic model based on 5 genes proved to be a reliable predictor of OA."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Five cellular senescence-associated biomarkers, BCL6, MCL1, SLC16A7, PIM1, and EPHA3, were identified and combined in a reliable nomogram-based diagnostic model for osteoarthritis.", "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:38268862"], "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:GSE12021"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_wilcoxon", "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:GSE12021"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38268862", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/IJGM.S447035", "sha256": "sha256:dcb690a56b22f099dbeeaeec702b81b1ed01e40b2b8208a5d42bebc1693f2d54", "bytes": 59312, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.2147/IJGM.S447035", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10807283", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE12021", "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=GSE12021", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE12021", "version": null, "note": "The datasets used in this investigation are available in internet sources. Below, you can find the names of the repository/repositories together with their corresponding accession number(s). The provided URL leads to the National Centre for Biotechnology Information (NCBI) website, GSE55235, GSE55457, GSE82107, GSE12021, and GSE51588. Cellular senescence-related genes (CSRGs) can be download from CellAge database: https://genomics.senescence.info/cells/query.php. The original images of the cell experiments in the article can be accessed at the following link: 10.6084/m9.figshare.24328570", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used in this investigation are available in internet sources. Below, you can find the names of the repository/repositories together with their corresponding accession number(s). The provided URL leads to the National Centre for Biotechnology Information (NCBI) website, GSE55235, GSE55457, GSE82107, GSE12021, and GSE51588. Cellular senescence-related genes (CSRGs) can be download from CellAge database: https://genomics.senescence.info/cells/query.php. The original images of the cell experiments in the article can be accessed at the following link: 10.6084/m9.figshare.24328570", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM302859", "GSM302864", "GSM302866", "GSM302870", "GSM302872", "GSM302874", "GSM302876", "GSM302878", "GSM302880", "GSM302881", "GSM302882", "GSM302895", "GSM302896", "GSM302897", "GSM302900", "GSM302905", "GSM302924", "GSM302926", "GSM302927", "GSM302929", "GSM302930", "GSM302932", "GSM302933", "GSM302934", "GSM302943", "GSM302944", "GSM303326", "GSM303339", "GSM303341", "GSM303355", "GSM303356", "GSM303357", "GSM303358", "GSM303359", "GSM303360", "GSM303361", "GSM303362", "GSM303363", "GSM303364", "GSM303365", "GSM303366", "GSM303367", "GSM303368", "GSM303369", "GSM303370", "GSM303377", "GSM303520", "GSM303521", "GSM303522", "GSM303523", "GSM303524", "GSM303525", "GSM303530", "GSM303531", "GSM303532", "GSM303533", "GSM303534"], "sample_count": 57, "group_sizes": null, "group_sizes_basis": null, "platform": "96;97", "taxon": "Homo sapiens", "title": "Identification of inter-individual and gene-specific variances in mRNA expression profiles in the RA SM", "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:GSE51588", "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=GSE51588", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE51588", "version": null, "note": "The datasets used in this investigation are available in internet sources. Below, you can find the names of the repository/repositories together with their corresponding accession number(s). The provided URL leads to the National Centre for Biotechnology Information (NCBI) website, GSE55235, GSE55457, GSE82107, GSE12021, and GSE51588. Cellular senescence-related genes (CSRGs) can be download from CellAge database: https://genomics.senescence.info/cells/query.php. The original images of the cell experiments in the article can be accessed at the following link: 10.6084/m9.figshare.24328570", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used in this investigation are available in internet sources. Below, you can find the names of the repository/repositories together with their corresponding accession number(s). The provided URL leads to the National Centre for Biotechnology Information (NCBI) website, GSE55235, GSE55457, GSE82107, GSE12021, and GSE51588. Cellular senescence-related genes (CSRGs) can be download from CellAge database: https://genomics.senescence.info/cells/query.php. The original images of the cell experiments in the article can be accessed at the following link: 10.6084/m9.figshare.24328570", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1248759", "GSM1248760", "GSM1248761", "GSM1248762", "GSM1248763", "GSM1248764", "GSM1248765", "GSM1248766", "GSM1248767", "GSM1248768", "GSM1248769", "GSM1248770", "GSM1248771", "GSM1248772", "GSM1248773", "GSM1248774", "GSM1248775", "GSM1248776", "GSM1248777", "GSM1248778", "GSM1248779", "GSM1248780", "GSM1248781", "GSM1248782", "GSM1248783", "GSM1248784", "GSM1248785", "GSM1248786", "GSM1248787", "GSM1248788", "GSM1248789", "GSM1248790", "GSM1248791", "GSM1248792", "GSM1248793", "GSM1248794", "GSM1248795", "GSM1248796", "GSM1248797", "GSM1248798", "GSM1248799", "GSM1248800", "GSM1248801", "GSM1248802", "GSM1248803", "GSM1248804", "GSM1248805", "GSM1248806", "GSM1248807", "GSM1248808"], "sample_count": 50, "group_sizes": null, "group_sizes_basis": null, "platform": "13497", "taxon": "Homo sapiens", "title": "Genome-wide Expression Profiles of Subchondral Bone in Osteoarthritis", "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:GSE55235", "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=GSE55235", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE55235", "version": null, "note": "The datasets used in this investigation are available in internet sources. Below, you can find the names of the repository/repositories together with their corresponding accession number(s). The provided URL leads to the National Centre for Biotechnology Information (NCBI) website, GSE55235, GSE55457, GSE82107, GSE12021, and GSE51588. Cellular senescence-related genes (CSRGs) can be download from CellAge database: https://genomics.senescence.info/cells/query.php. The original images of the cell experiments in the article can be accessed at the following link: 10.6084/m9.figshare.24328570", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used in this investigation are available in internet sources. Below, you can find the names of the repository/repositories together with their corresponding accession number(s). The provided URL leads to the National Centre for Biotechnology Information (NCBI) website, GSE55235, GSE55457, GSE82107, GSE12021, and GSE51588. Cellular senescence-related genes (CSRGs) can be download from CellAge database: https://genomics.senescence.info/cells/query.php. The original images of the cell experiments in the article can be accessed at the following link: 10.6084/m9.figshare.24328570", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1332201", "GSM1332202", "GSM1332203", "GSM1332204", "GSM1332205", "GSM1332206", "GSM1332207", "GSM1332208", "GSM1332209", "GSM1332210", "GSM1332211", "GSM1332212", "GSM1332213", "GSM1332214", "GSM1332215", "GSM1332216", "GSM1332217", "GSM1332218", "GSM1332219", "GSM1332220", "GSM1332221", "GSM1332222", "GSM1332223", "GSM1332224", "GSM1332225", "GSM1332226", "GSM1332227", "GSM1332228", "GSM1332229", "GSM1332230"], "sample_count": 30, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "Identification of rheumatoid arthritis and osteoarthritis patients by transcriptome-based rule set generation", "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:GSE55457", "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=GSE55457", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE55457", "version": null, "note": "The datasets used in this investigation are available in internet sources. Below, you can find the names of the repository/repositories together with their corresponding accession number(s). The provided URL leads to the National Centre for Biotechnology Information (NCBI) website, GSE55235, GSE55457, GSE82107, GSE12021, and GSE51588. Cellular senescence-related genes (CSRGs) can be download from CellAge database: https://genomics.senescence.info/cells/query.php. The original images of the cell experiments in the article can be accessed at the following link: 10.6084/m9.figshare.24328570", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used in this investigation are available in internet sources. Below, you can find the names of the repository/repositories together with their corresponding accession number(s). The provided URL leads to the National Centre for Biotechnology Information (NCBI) website, GSE55235, GSE55457, GSE82107, GSE12021, and GSE51588. Cellular senescence-related genes (CSRGs) can be download from CellAge database: https://genomics.senescence.info/cells/query.php. The original images of the cell experiments in the article can be accessed at the following link: 10.6084/m9.figshare.24328570", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1337304", "GSM1337305", "GSM1337306", "GSM1337307", "GSM1337308", "GSM1337309", "GSM1337310", "GSM1337311", "GSM1337312", "GSM1337313", "GSM1337314", "GSM1337315", "GSM1337316", "GSM1337317", "GSM1337318", "GSM1337319", "GSM1337320", "GSM1337321", "GSM1337322", "GSM1337323", "GSM1337324", "GSM1337325", "GSM1337326", "GSM1337327", "GSM1337328", "GSM1337329", "GSM1337330", "GSM1337331", "GSM1337332", "GSM1337333", "GSM1337334", "GSM1337335", "GSM1337336"], "sample_count": 33, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "Identification of rheumatoid arthritis and osteoarthritis patients by transcriptome-based rule set generation [Jena]", "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:GSE82107", "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=GSE82107", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE82107", "version": null, "note": "The datasets used in this investigation are available in internet sources. Below, you can find the names of the repository/repositories together with their corresponding accession number(s). The provided URL leads to the National Centre for Biotechnology Information (NCBI) website, GSE55235, GSE55457, GSE82107, GSE12021, and GSE51588. Cellular senescence-related genes (CSRGs) can be download from CellAge database: https://genomics.senescence.info/cells/query.php. The original images of the cell experiments in the article can be accessed at the following link: 10.6084/m9.figshare.24328570", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used in this investigation are available in internet sources. Below, you can find the names of the repository/repositories together with their corresponding accession number(s). The provided URL leads to the National Centre for Biotechnology Information (NCBI) website, GSE55235, GSE55457, GSE82107, GSE12021, and GSE51588. Cellular senescence-related genes (CSRGs) can be download from CellAge database: https://genomics.senescence.info/cells/query.php. 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE55235", "GSE55457", "GSE82107", "GSE12021", "GSE51588"], "resolved_accessions": ["GSE55235", "GSE55457", "GSE82107", "GSE12021", "GSE51588"], "statements": ["The datasets used in this investigation are available in internet sources. Below, you can find the names of the repository/repositories together with their corresponding accession number(s). The provided URL leads to the National Centre for Biotechnology Information (NCBI) website, GSE55235, GSE55457, GSE82107, GSE12021, and GSE51588. Cellular senescence-related genes (CSRGs) can be download from CellAge database: https://genomics.senescence.info/cells/query.php. The original images of the cell experiments in the article can be accessed at the following link: 10.6084/m9.figshare.24328570"], "basis": "The paper names GSE55235, GSE55457, GSE82107, GSE12021, GSE51588 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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Results: Five genes (BC", "from healthy synovial tissue of experimental rats, was obtained from Saibaikang (Shanghai, Chi"], "order_basis": "paper_text_order:1086", "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": ["e cells and the biomarkers. Cell Culture and Transfection The RPKFCL, derived from healthy synovial ti", "ctor and used to introduce it into RPKFCL by transfection. Perform the transfection of the lentiviral", "it into RPKFCL by transfection. Perform the transfection of the lentiviral vector containing overexpr", "argeted cells, and the effectiveness of PIM1 transfection was confirmed using q-PCR analysis. Statisti"], "order_basis": "paper_text_order:3106", "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": 0.77, "evidence": ["Saibaikang (Shanghai, China). The cells were cultured in Fibroblast medium supplemented with 10% feta"], "order_basis": "paper_text_order:3253", "id": "assay:3"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Wilcoxon"], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}