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pmid:34488536

Comprehensive analysis of pivotal biomarkers, immune cell infiltration and therapeutic drugs for steroid-induced osteonecrosis of the femoral head.

Bo Wang · Song Gong · Wenkai Shao · Lizhi Han · Zilin Li · Zhichao Zhang · Yang Zheng · Fang Ouyang · Yan Ma · Weihua Xu · Yong Feng

Bioengineered · 2021 doi:10.1080/21655979.2021.1972081

Paper

complete

Experiment

complete

Data

partial

Analysis

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Execution

absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:34488536
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science-record
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paper object · 10 fields
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title
Comprehensive analysis of pivotal biomarkers, immune cell infiltration and therapeutic drugs for steroid-induced osteonecrosis of the femoral head.
doi
10.1080/21655979.2021.1972081
pmid
34488536
authors array · 11 items
[0]
Bo Wang
[1]
Song Gong
[2]
Wenkai Shao
[3]
Lizhi Han
[4]
Zilin Li
[5]
Zhichao Zhang
[6]
Yang Zheng
[7]
Fang Ouyang
[8]
Yan Ma
[9]
Weihua Xu
[10]
Yong Feng
journal
Bioengineered
year
2021
abstract
Steroid-induced osteonecrosis of the femoral head (SONFH) is a progressive disease that leads to an increased disability rate. This study aimed to ascertain biomarkers, infiltrating immune cells, and therapeutic drugs for SONFH. The gene expression profile of the GSE123568 dataset was downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified using the NetworkAnalyst platform. Functional enrichment, protein-protein interaction network (PPI), and module analyses were performed using Metascape tools. An immune cell abundance identifier was used to explore immune cell infiltration. Furthermore, hub genes were identified based on maximal clique centrality (MCC) evaluation using cytoHubba application and confirmed by qRT-PCR using clinical samples. Finally, the L1000 platform was used to determine potential drugs for SONFH treatment. The SONFH mouse model was used to determine the therapeutic effects of aspirin. In total, 429 DEGs were identified in SONFH samples. Functional enrichment analysis showed that these DEGs were enriched in myeloid leukocyte activation and osteoclast differentiation processes. A set of nine immune cell types was confirmed to be markedly different between the SONFH and control samples. All 10 hub genes were significantly highly expressed in the serum of SONFH patients, as shown by qRT-PCR. Finally, the therapeutic effect of aspirin on SONFH was examined in animal experiments. Taken together, our data revealed the hub genes and infiltrating immune cells in SONFH, and we also screened potential drugs for use in SONFH treatment.
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All the data in our study will be made available by the authors upon reasonable request. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE123568
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title
Identification of Potential Biomarkers for Improving the Precision of Early Detection of Steroid-induced Osteonecrosis of the Femoral Head
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Functional enrichment analysis and PPI network construction
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The six most significant MCODE components were extracted from the PPI
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The top 10 compounds with activity against SONFH as predicted via connectivity map
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Prediction of potential therapeutic drugs for SONFH
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Table 2.
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The top 10 compounds with activity against SONFH as predicted via connectivity map
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All the data in our study will be made available by the authors upon reasonable request. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE123568
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tential drugs for SONFH treatment. The SONFH mouse model was used to determine the therapeutic effect
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tential drugs for SONFH treatment. The SONFH mouse model was used to determine the therapeutic
[2]
necrosis [23]. At the end of the treatment, mice were sacrificed and samples of the femoral head were obtaine
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weeks. For the GC+ aspirin treatment group, mice were treated with aspirin (10 mg/kg) daily via ga
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34488536", "kind": "science-record", "revision": 8, "content_hash": "sha256:f73d3bdb10be7b1f2393092c63a0b23799dae6820a6b03ef1a93fc5562c26495", "created_at": "2026-11-01T15:41:50Z", "updated_at": "2026-11-01T22:47:27Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Comprehensive analysis of pivotal biomarkers, immune cell infiltration and therapeutic drugs for steroid-induced osteonecrosis of the femoral head.", "doi": "10.1080/21655979.2021.1972081", "pmid": "34488536", "authors": ["Bo Wang", "Song Gong", "Wenkai Shao", "Lizhi Han", "Zilin Li", "Zhichao Zhang", "Yang Zheng", "Fang Ouyang", "Yan Ma", "Weihua Xu", "Yong Feng"], "journal": "Bioengineered", "year": 2021, "abstract": "Steroid-induced osteonecrosis of the femoral head (SONFH) is a progressive disease that leads to an increased disability rate. This study aimed to ascertain biomarkers, infiltrating immune cells, and therapeutic drugs for SONFH. The gene expression profile of the GSE123568 dataset was downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified using the NetworkAnalyst platform. Functional enrichment, protein-protein interaction network (PPI), and module analyses were performed using Metascape tools. An immune cell abundance identifier was used to explore immune cell infiltration. Furthermore, hub genes were identified based on maximal clique centrality (MCC) evaluation using cytoHubba application and confirmed by qRT-PCR using clinical samples. Finally, the L1000 platform was used to determine potential drugs for SONFH treatment. The SONFH mouse model was used to determine the therapeutic effects of aspirin. In total, 429 DEGs were identified in SONFH samples. Functional enrichment analysis showed that these DEGs were enriched in myeloid leukocyte activation and osteoclast differentiation processes. A set of nine immune cell types was confirmed to be markedly different between the SONFH and control samples. All 10 hub genes were significantly highly expressed in the serum of SONFH patients, as shown by qRT-PCR. Finally, the therapeutic effect of aspirin on SONFH was examined in animal experiments. Taken together, our data revealed the hub genes and infiltrating immune cells in SONFH, and we also screened potential drugs for use in SONFH treatment.", "claims": [{"id": "claim-method", "statement": "Statistical significance was determined using a two-tailed Student’s t-test when two groups were compared, and one-way ANOVA was followed by Bonferroni’s post hoc test when comparing more than two groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34488536", "locator": "sections[10] \"Statistical analysis\" paragraph 2", "quote": "Statistical significance was determined using a two-tailed Student’s t-test when two groups were compared, and one-way ANOVA was followed by Bonferroni’s post hoc test when comparing more than two groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All the data in our study will be made available by the authors upon reasonable request. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE123568", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34488536", "locator": "sections[22] \"Data availability statement\" paragraph 2", "quote": "All the data in our study will be made available by the authors upon reasonable request. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE123568"}], "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:34488536"], "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:GSE123568"], "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:GSE123568"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34488536", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1080/21655979.2021.1972081", "sha256": 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"group_sizes_basis": null, "platform": "15207", "taxon": "Homo sapiens", "title": "Identification of Potential Biomarkers for Improving the Precision of Early Detection of Steroid-induced Osteonecrosis of the Femoral Head", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:34488536:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ff66f9606bd8b042c863b5550407fa228dee5b3edb0cd07e847c1db7a29ad051", "bytes": 1183, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#t0001", "version": null, "note": "The six most significant MCODE components were extracted from the PPI", "structure": {"pmcid": "PMC8815624", "section_index": 13, "section_title": "Functional enrichment analysis and PPI network construction", "row_count": 7, "column_count": 2}, "table": {"label": "Table 1.", "caption": "The six most significant MCODE components were extracted from the PPI", "rows": [["MCODE_ALL", "R-HSA-373076 Class A/1 (Rhodopsin-like receptors);R-HSA-500792 GPCR ligand binding;GO:0002274 myeloid leukocyte activation"], ["MCODE_1", "GO:0042026 protein refolding;GO:0019320 hexose catabolic process;hsa00010 Glycolysis/Gluconeogenesis"], ["MCODE_2", "R-HSA-373076 Class A/1 (Rhodopsin-like receptors);R-HSA-418594 G alpha (i) signaling events;R-HSA-500792 GPCR ligand binding"], ["MCODE_3", "GO:0002755 MyD88-dependent toll-like receptor signaling pathway;GO:0032757 positive regulation of interleukin-8 production; GO:0032677 regulation of interleukin-8 production"], ["MCODE_4", "R-HSA-416476 G alpha (q) signaling events;R-HSA-373076 Class A/1 (Rhodopsin-like receptors);R-HSA-500792 GPCR ligand binding"], ["MCODE_5", "GO:0008285 negative regulation of cell proliferation"], ["MCODE_6", "GO:0045669 positive regulation of osteoblast differentiation; GO:0045778 positive regulation of ossification;GO:0045667 regulation of osteoblast differentiation"]], "row_count": 7, "column_count": 2, "numeric_cells": 13, "header_rows": 1, "locator": "section[13]/table-wrap[1]#t0001"}}, {"id": "asset:table:pmid:34488536:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:7f50595b15f9728a11b209500f810689aa89dcc3a9e29b8590e32b10a52dc3bc", "bytes": 1253, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[16]/table-wrap[1]#t0002", "version": null, "note": "The top 10 compounds with activity against SONFH as predicted via connectivity map", "structure": {"pmcid": "PMC8815624", "section_index": 16, "section_title": "Prediction of potential therapeutic drugs for SONFH", "row_count": 11, "column_count": 4}, "table": {"label": "Table 2.", "caption": "The top 10 compounds with activity against SONFH as predicted via connectivity map", "rows": [["Score", "Name", "Description", "Target"], ["−99.68", "Phylloquinone", "Vitamin K", "BGLAP, GGCX"], ["−99.58", "cholic-acid", "Bile acid", "ADH1C, CES1, COX4I1, COX5A, COX5B, COX6A2, COX6B1, COX6C, COX7A1, COX7B, COX7C, COX8A, ESRRG, FABP6, FECH, GPBAR1, MT-CO1, MT-CO2, MT-CO3, PLA2G1B"], ["−99.58", "MRS-1220", "Adenosine receptor antagonist", "ADORA2B, ADORA3"], ["−99.54", "Bucladesine", "Adenosine receptor agonist", "PRKACA"], ["−99.51", "Isotretinoin", "Retinoid receptor agonist", "CYP2B6, CYP2C19, CYP2C8, CYP3A5, CYP3A7, NR2C2, PPARD, RARA, RARB, RARG, RORB"], ["−99.22", "Doxercalciferol", "Vitamin D receptor agonist", "VDR"], ["−98.8", "Betahistine", "Histamine receptor agonist", "HRH1, HRH3"], ["−98.8", "Aspirin", "Cyclooxygenase inhibitor", "AKR1C1, ASIC3, EDNRA, HSPA5, IKBKB, NFKB1, NFKB2, NFKBIA, PRKAA1, PRKAA2, PRKAB1, PRKAB2, PRKAG1, PRKAG2, PRKAG3, PTGS1, PTGS2, RPS6KA3, TP53"], ["−98.73", 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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": ["GSE123568"], "resolved_accessions": ["GSE123568"], "statements": ["All the data in our study will be made available by the authors upon reasonable request. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE123568"], "basis": "The paper names GSE123568 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": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "assets": ["source:pmid:34488536", "data:geo:GSE123568", "asset:table:pmid:34488536:1", "asset:table:pmid:34488536:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE123568"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:34:30Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 23924, "completion_tokens": 1493, "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:34488536", "type": "paper", "label": "pmid:34488536"}, {"id": "source:pmid:34488536", "type": "manuscript", "label": "PMID 34488536 full text"}, {"id": "data:geo:GSE123568", "type": "dataset", "label": "GEO GSE123568"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34488536", "type": "paper", "label": "pmid:34488536"}, {"id": "source:pmid:34488536", "type": "manuscript", "label": "PMID 34488536 full text"}, {"id": "data:geo:GSE123568", "type": "dataset", "label": "GEO GSE123568"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34488536", "type": "extraction", "used": ["source:pmid:34488536"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE123568", "type": "accession_resolution", "used": ["data:geo:GSE123568"], "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:34488536", "parent_hash": "sha256:b110f804c3777dc96d5db60cf6867c9fe0a3d679c4299aca9c36fdae19c21df4", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE123568 licence not read", "asset:data:geo:GSE123568 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["tential drugs for SONFH treatment. The SONFH mouse model was used to determine the therapeutic effect", "tential drugs for SONFH treatment. The SONFH mouse model was used to determine the therapeutic", "necrosis [23]. At the end of the treatment, mice were sacrificed and samples of the femoral head were obtaine", "weeks. For the GC+ aspirin treatment group, mice were treated with aspirin (10 mg/kg) daily via ga"], "order_basis": "paper_text_order:1013", "id": "assay:1"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Statistical significance was determined using a two-tailed Student’s t-test when two groups were compared, and one-way ANOVA was followed by Bonferroni’s post hoc test when comparing more than two groups."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}