Identification and analysis of mitochondria-related central genes in steroid-induced osteonecrosis of the femoral head, along with drug prediction.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38384969", "kind": "science-record", "revision": 4, "content_hash": "sha256:c1dc016c2cf47a4dff0103f92e953a14a3b696829a6b25a4b573a4001eec5a3f", "created_at": "2026-11-01T19:20:19Z", "updated_at": "2026-11-01T22:53:44Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and analysis of mitochondria-related central genes in steroid-induced osteonecrosis of the femoral head, along with drug prediction.", "doi": "10.3389/fendo.2024.1341366", "pmid": "38384969", "authors": ["Zheru Ma", "Jing Sun", "Qi Jiang", "Yao Zhao", "Haozhuo Jiang", "Peng Sun", "Wei Feng"], "journal": "Frontiers in endocrinology", "year": 2024, "abstract": "Purpose: Steroid-induced osteonecrosis of the femoral head (SONFH) is a refractory orthopedic hip joint disease that primarily affects middle-aged and young individuals. SONFH may be caused by ischemia and hypoxia of the femoral head, where mitochondria play a crucial role in oxidative reactions. Currently, there is limited literature on whether mitochondria are involved in the progression of SONFH. Here, we aim to identify and validate key potential mitochondrial-related genes in SONFH through bioinformatics analysis. This study aims to provide initial evidence that mitochondria play a role in the progression of SONFH and further elucidate the mechanisms of mitochondria in SONFH.\nMethods: The GSE123568 mRNA expression profile dataset includes 10 non-SONFH (non-steroid-induced osteonecrosis of the femoral head) samples and 30 SONFH samples. The GSE74089 mRNA expression profile dataset includes 4 healthy samples and 4 samples with ischemic necrosis of the femoral head. Both datasets were downloaded from the Gene Expression Omnibus (GEO) database. The mitochondrial-related genes are derived from MitoCarta3.0, which includes data for all 1136 human genes with high confidence in mitochondrial localization based on integrated proteomics, computational, and microscopy approaches. By intersecting the GSE123568 and GSE74089 datasets with a set of mitochondrial-related genes, we screened for mitochondrial-related genes involved in SONFH. Subsequently, we used the good Samples Genes method in R language to remove outlier genes and samples in the GSE123568 dataset. We further used WGCNA to construct a scale-free co-expression network and selected the hub gene set with the highest connectivity. We then intersected this gene set with the previously identified mitochondrial-related genes to select the genes with the highest correlation. A total of 7 mitochondrial-related genes were selected. Next, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the selected mitochondrial-related genes using R software. Furthermore, we performed protein network analysis on the differentially expressed proteins encoded by the mitochondrial genes using STRING. We used the GSEA software to group the genes within the gene set in the GSE123568 dataset based on their coordinated changes and evaluate their impact on phenotype changes. Subsequently, we grouped the samples based on the 7 selected mitochondrial-related genes using R software and observed the differences in immune cell infiltration between the groups. Finally, we evaluated the prognostic significance of these features in the two datasets, consisting of a total of 48 samples, by integrating disease status and the 7 gene features using the cox method in the survival R package. We performed ROC analysis using the roc function in the pROC package and evaluated the AUC and confidence intervals using the ci function to obtain the final AUC results.\nResults: Identification and analysis of 7 intersecting DEGs (differentially expressed genes) were obtained among peripheral blood, cartilage samples, hub genes, and mitochondrial-related genes. These 7 DEGs include FTH1, LACTB, PDK3, RAB5IF, SOD2, and SQOR, all of which are upregulated genes with no intersection in the downregulated gene set. Subsequently, GO and KEGG pathway enrichment analysis revealed that the upregulated DEGs are primarily involved in processes such as oxidative stress, release of cytochrome C from mitochondria, negative regulation of intrinsic apoptotic signaling pathway, cell apoptosis, mitochondrial metabolism, p53 signaling pathway, and NK cell-mediated cytotoxicity. GSEA also revealed enriched pathways associated with hub genes. Finally, the diagnostic value of these key genes for hormone-related ischemic necrosis of the femoral head (SONFH) was confirmed using ROC curves.\nConclusion: BID, FTH1, LACTB, PDK3, RAB5IF, SOD2, and SQOR may serve as potential diagnostic mitochondrial-related biomarkers for SONFH. Additionally, they hold research value in investigating the involvement of mitochondria in the pathogenesis of ischemic necrosis of the femoral head.", "claims": [{"id": "claim-method", "statement": "Differential gene expression analysis was conducted using the “limma” software package in R: Genes meeting the criteria of p_adj <0.01 and abs |log2 fold change (FC)|> log21.5 were considered as differentially expressed genes (DEGs), indicating their potential significance in the study.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38384969", "locator": "sections[2] \"Materials and methods\" paragraph 5", "quote": "Differential gene expression analysis was conducted using the “limma” software package in R: Genes meeting the criteria of p_adj <0.01 and abs |log2 fold change (FC)|> log21.5 were considered as differentially expressed genes (DEGs), indicating their potential significance in the study."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38384969", "locator": "sections[12] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "BID, FTH1, LACTB, PDK3, RAB5IF, SOD2, and SQOR may serve as potential diagnostic mitochondrial-related biomarkers for SONFH.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38384969", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "BID, FTH1, LACTB, PDK3, RAB5IF, SOD2, and SQOR may serve as potential diagnostic mitochondrial-related biomarkers for SONFH."}, {"asset": "source:pmid:38384969", "locator": "sections[4] \"Identification of hub genes\" paragraph 2", "quote": "By intersecting the 1,924 DEGs from GSE123568, 5,438 DEGs from GSE74089, 751 genes from the tan module, and 1,136 mitochondria-related genes, we identified 7 mitochondria-related hub genes associated with SONFH ( Figure 4 ), including BID, FTH1, LACTB, PDK3, RAB5IF, SOD2, and SQOR."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "BID, FTH1, LACTB, PDK3, RAB5IF, SOD2, and SQOR may serve as potential diagnostic mitochondrial-related biomarkers for SONFH.", "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:38384969"], "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:38384969", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fendo.2024.1341366", "sha256": "sha256:5403dd2fa1850a9cddc9837a1b1243809d7b9b274657461a5406258bb6da76df", "bytes": 76251, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fendo.2024.1341366", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10879930", "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": "The original contributions presented in the study are included in the article/ Supplementary Material . 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