A diagnostic signatures for intervertebral disc degeneration using TNFAIP6 and COL6A2 based on single-cell RNA-seq and bulk RNA-seq analyses.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39704340", "kind": "science-record", "revision": 3, "content_hash": "sha256:fa5f93db4e9a48b09dba2663a157e2817b2f7b390226f89ef25883d5eac22f7f", "created_at": "2026-11-01T20:30:01Z", "updated_at": "2026-11-01T22:13:24Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A diagnostic signatures for intervertebral disc degeneration using TNFAIP6 and COL6A2 based on single-cell RNA-seq and bulk RNA-seq analyses.", "doi": "10.1080/07853890.2024.2443568", "pmid": "39704340", "authors": ["Hong-Mei Song", "Zuo-Wei Li", "Qin Huang", "Chun-Gen Wu", "Ming-Hua Li", "Jun-Kang Shen"], "journal": "Annals of medicine", "year": 2025, "abstract": "OBJECTIVES: Intervertebral disc degeneration (IVDD) is a prevalent degenerative condition associated with a high incidence rate of low back pain and disability. This study aimed to identify potential biomarkers and signaling pathways associated with IVDD.\nMETHODS: Biomarkers were discerned through bulk-RNA and single-cell RNA sequencing (scRNA-Seq) investigations of IVDD cases from the Gene Expression Omnibus (GEO) database. Following this, two central genes were identified. Furthermore, gene set enrichment analysis (GSEA) and receiver operating characteristic (ROC) curve analysis were conducted. The transcriptional factor (TF) derived from nucleus pulposus (NP) cells was examined through the DoRothEA R package. RT-qPCR and IHC techniques were employed to confirm the expression of the two hub genes and their associated genes in tissue samples.\nRESULTS: The proteins Tumor necrosis factor-inducible gene 6 protein (TNFAIP6) and collagen VI-α2 (COL6A2) were frequently analyzed using a combination of DEGs from datasets GSE70362, GSE124272, and scRNA-seq. Examination of gene expression across multiple datasets indicated significant differences in TNFAIP6 and COL6A2 levels in IVDD compared to control or normal groups (p < 0.05). These two central genes demonstrated strong diagnostic utility in the training cohort and reliable predictive value in the validation datasets. Our study verified the potential role of ZEB2 as a TF in regulating two key genes associated with IVDD. Furthermore, qPCR and IHC confirmed elevated expression levels of the hub genes and transcription factor.\nCONCLUSION: We identified biomarkers, specifically TNFAIP6 and COL6A2, that have the potential to predict disease activity and aid in the diagnosis of IVDD.", "claims": [{"id": "claim-method", "statement": "The diagnostic performance of the model was assessed through the analysis of receiver operating characteristic (ROC) curves and calculation of the area under the curve (AUC) using a generalized linear model.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39704340", "locator": "sections[8] \"Selection of hub genes, model construction and nomogram establishment\" paragraph 2", "quote": "The diagnostic performance of the model was assessed through the analysis of receiver operating characteristic (ROC) curves and calculation of the area under the curve (AUC) using a generalized linear model."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The authors declare that all relevant data supporting the findings presented in this study are available within the article and its Supplementary Information files, or, from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39704340", "locator": "sections[32] \"Data availability\" paragraph 2", "quote": "The authors declare that all relevant data supporting the findings presented in this study are available within the article and its Supplementary Information files, or, from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The two central genes demonstrated strong diagnostic utility in the training cohort and reliable predictive value in the validation datasets.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39704340", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "These two central genes demonstrated strong diagnostic utility in the training cohort and reliable predictive value in the validation datasets."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The two central genes demonstrated strong diagnostic utility in the training cohort and reliable predictive value in the validation datasets.", "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:39704340"], "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. 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Examination of gene expression across multi"], "order_basis": "paper_text_order:50", "id": "assay:1"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["sing TNFAIP6 and COL6A2 based on single-cell RNA-seq and bulk RNA-seq analyses.", "COL6A2 based on single-cell RNA-seq and bulk RNA-seq analyses.", "e discerned through bulk-RNA and single-cell RNA sequencing (scRNA-Seq) investigations of IVDD cases fro"], "order_basis": "paper_text_order:62", "id": "assay:2"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["was examined through the DoRothEA R package. RT-qPCR and IHC techniques were employed to confirm", "examined through the DoRothEA R package. RT-qPCR and IHC techniques were employed to confirm", "key genes associated with IVDD. Furthermore, qPCR and IHC confirmed elevated expression levels", "ignificant role in the IVDD process. Through RT-qPCR analysis of IVDD tissue samples, we observed"], "order_basis": "paper_text_order:819", "id": "assay:3"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["through the DoRothEA R package. RT-qPCR and IHC techniques were employed to confirm the expr", "associated with IVDD. Furthermore, qPCR and IHC confirmed elevated expression levels of the", "rvertebral disc degeneration (IVDD) tissues, immunohistochemical staining was conducted on tissue sections to", "ssion of IVDD Verification of four genes for IHC.(A-D) IHC for IL-1β, ZEB2, TNFAIP6 and COL6A"], "order_basis": "paper_text_order:832", "id": "assay:4"}, {"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:5"}]}