Identification of potential autophagy-related genes in steroid-induced osteonecrosis of the femoral head via bioinformatics analysis and experimental verification.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35151359", "kind": "science-record", "revision": 5, "content_hash": "sha256:aac18c574fe6cac805e81ab399b21ef00bf58e24ec5b40fc524324494bb7d4e8", "created_at": "2026-11-01T17:36:54Z", "updated_at": "2026-11-01T22:48:27Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of potential autophagy-related genes in steroid-induced osteonecrosis of the femoral head via bioinformatics analysis and experimental verification.", "doi": "10.1186/s13018-022-02977-x", "pmid": "35151359", "authors": ["Xue-Zhen Liang", "Di Luo", "Yan-Rong Chen", "Jia-Cheng Li", "Bo-Zhao Yan", "Yan-Bo Guo", "Ming-Tao Wen", "Bo Xu", "Gang Li"], "journal": "Journal of orthopaedic surgery and research", "year": 2022, "abstract": "PURPOSE: Steroid-induced osteonecrosis of the femoral head (SONFH) is a refractory orthopaedic hip joint disease that occurs in young- and middle-aged people. Previous experimental studies have shown that autophagy might be involved in the pathological process of SONFH, but the pathogenesis of autophagy in SONFH remains unclear. We aimed to identify and validate the key potential autophagy-related genes involved in SONFH to further illustrate the mechanism of autophagy in SONFH through bioinformatics analysis.\nMETHODS: The GSE123568 mRNA expression profile dataset, including 10 non-SONFH (following steroid administration) samples and 30 SONFH samples, was downloaded from the Gene Expression Omnibus (GEO) database. Autophagy-related genes were obtained from the Human Autophagy Database (HADb). The autophagy-related genes involved in SONFH were screened by intersecting the GSE123568 dataset with the set of autophagy genes. The differentially expressed autophagy-related genes involved in SONFH were identified with R software. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially expressed autophagy-related genes involved in SONFH were conducted by using R software. Then, the correlations between the expression levels of the differentially expressed autophagy-related genes involved in SONFH were confirmed with R software. Moreover, the protein-protein interaction (PPI) network was analysed by using the Search Tool for the Retrieval of Interacting Genes (STRING), significant gene cluster modules were identified with the MCODE Cytoscape plugin, and hub genes among the differentially expressed autophagy-related genes involved in SONFH were screened by using the CytoHubba Cytoscape plugin. Finally, the expression levels of the hub genes of the differentially expressed autophagy-related genes involved in SONFH were validated in hip articular cartilage specimens from necrotic femur heads (NFHs) by using the GSE74089 dataset and further verification by qRT-PCR.\nRESULTS: A total of 34 differentially expressed autophagy-related genes were identified between the peripheral blood samples of SONFH patients and non-SONFH patients based on the defined criteria, including 25 upregulated genes and 9 downregulated genes. The GO and KEGG pathway enrichment analyses revealed that these 34 differentially expressed autophagy-related genes involved in SONFH were particularly enriched in death domain receptors, the FOXO signalling pathway and apoptosis. Correlation analysis revealed significant correlations among the 34 differentially expressed autophagy-related genes involved in SONFH. The PPI results demonstrated that the 34 differentially expressed autophagy-related genes interacted with each other. Ten hub genes were identified by using the MCC algorithms of CytoHubba. The GSE74089 dataset showed that TNFSF10, PTEN and CFLAR were significantly upregulated while BCL2L1 was significantly downregulated in the hip cartilage specimens, which was consistent with the GSE123568 dataset. TNFSF10, PTEN and BCL2L1 were detected with consistent expression by qRT-PCR.\nCONCLUSIONS: Thirty-four potential autophagy-related genes involved in SONFH were identified via bioinformatics analysis. TNFSF10, PTEN and BCL2L1 might serve as potential drug targets and biomarkers because they regulate autophagy. These results expand the autophagy-related understanding of SONFH and might be useful in the diagnosis and prognosis of SONFH.", "claims": [{"id": "claim-method", "statement": "To identify the differentially expressed autophagy-related genes in SONFH, we used the “limma” R package, and an adjusted P value < 0.05 and |log2 fold change (FC)|> log21.5 were the criteria for screening differentially expressed genes.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35151359", "locator": "sections[4] \"Differential expression analysis of autophagy-related genes in SONFH\" paragraph 2", "quote": "To identify the differentially expressed autophagy-related genes in SONFH, we used the “limma” R package, and an adjusted P value < 0.05 and |log2 fold change (FC)|> log21.5 were the criteria for screening differentially expressed genes."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analysed in this study. These datasets can be found at the following URLs: HADb (http://www.autophagy.lu/index.html), GSE123568 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE123568) and GSE74089 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE74089).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35151359", "locator": "sections[22] \"Availability of data and materials\" paragraph 2", "quote": "Publicly available datasets were analysed in this study. These datasets can be found at the following URLs: HADb (http://www.autophagy.lu/index.html), GSE123568 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE123568) and GSE74089 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE74089)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A total of 34 differentially expressed autophagy-related genes were identified between the peripheral blood samples of SONFH patients and non-SONFH patients based on the defined criteria, including 25 upregulated genes and 9 downregulated genes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35151359", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A total of 34 differentially expressed autophagy-related genes were identified between the peripheral blood samples of SONFH patients and non-SONFH patients based on the defined criteria, including 25 upregulated genes and 9 downregulated genes."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A total of 34 differentially expressed autophagy-related genes were identified between the peripheral blood samples of SONFH patients and non-SONFH patients based on the defined criteria, including 25 upregulated genes and 9 downregulated genes.", "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:35151359"], "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:35151359", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s13018-022-02977-x", "sha256": "sha256:a1e3d1fed3d4fc9e6dd72018cb673e1a6525ba3aeadc2abef74750ccbac3503e", "bytes": 45424, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s13018-022-02977-x", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8840318", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE123568", "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=GSE123568", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE123568", "version": null, "note": "Publicly available datasets were analysed in this study. These datasets can be found at the following URLs: HADb (http://www.autophagy.lu/index.html), GSE123568 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE123568) and GSE74089 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE74089).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analysed in this study. These datasets can be found at the following URLs: HADb (http://www.autophagy.lu/index.html), GSE123568 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE123568) and GSE74089 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE74089).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3507251", "GSM3507252", "GSM3507253", "GSM3507254", "GSM3507255", "GSM3507256", "GSM3507257", "GSM3507258", "GSM3507259", "GSM3507260", "GSM3507261", "GSM3507262", "GSM3507263", "GSM3507264", "GSM3507265", "GSM3507266", "GSM3507267", "GSM3507268", "GSM3507269", "GSM3507270", "GSM3507271", "GSM3507272", "GSM3507273", "GSM3507274", "GSM3507275", "GSM3507276", "GSM3507277", "GSM3507278", "GSM3507279", "GSM3507280", "GSM3507281", "GSM3507282", "GSM3507283", "GSM3507284", "GSM3507285", "GSM3507286", "GSM3507287", "GSM3507288", "GSM3507289", "GSM3507290"], "sample_count": 40, "group_sizes": null, "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": "data:geo:GSE74089", "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=GSE74089", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE74089", "version": null, "note": "Publicly available datasets were analysed in this study. These datasets can be found at the following URLs: HADb (http://www.autophagy.lu/index.html), GSE123568 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE123568) and GSE74089 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE74089).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analysed in this study. 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