Potential diagnostic and therapeutic gene in chronic low back pain through pyroptosis modulation: A silico study based on the dataset analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40670404", "kind": "science-record", "revision": 4, "content_hash": "sha256:50f9c2bbf369ba61905714dfcf93eb87323ad44ea5ea66bfc2b3c8710aae9c17", "created_at": "2026-11-01T20:30:46Z", "updated_at": "2026-11-01T22:56:51Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Potential diagnostic and therapeutic gene in chronic low back pain through pyroptosis modulation: A silico study based on the dataset analysis.", "doi": "10.1038/s41598-025-06756-6", "pmid": "40670404", "authors": ["Jintao Guo", "Tao Sun"], "journal": "Scientific reports", "year": 2025, "abstract": "Chronic low back pain (cLBP ) is a common condition that affects the quality of life, can be caused by disc degeneration, facet arthropathy, myofascial pain, sacroiliac joint pain, spondyloarthropathies, and nociplastic pain etc. Research suggests that excessive pyroptosis may trigger cytokine release and harmful inflammation, leading to tissue damage and organ dysfunction, which could be a potential molecular mechanism underlying these conditions. Our aim in this research was to look into the effects of genes associated with pyroptosis in cLBP, with the goal of describing possible markers for diagnosis and targets for treatment. A comprehensive analysis of Differentially Expressed Genes (DEGs) was performed utilizing the GSE177034 datasets sourced from the Gene Expression Omnibus (GEO) repository. GSE177034 included 98 patients admitted to the hospital for treatment of low back pain, all of whom had peripheral blood extracted and sequenced. We identified 883 DEGs, including 397 upregulated and 486 downregulated genes, in cLBP. The WGCNA revealed 11 co-expression modules, with the blue module presenting the utmost positive connection to pyroptosis. The GO and KEGG analyses showed that DEGs associated with pyroptosis were substantially enriched in pathways like the NF-kappaB transcription factor activity and the MyD88-dependent signaling pathway of Toll-like receptors. Machine learning approaches identified five pyroptosis relate hub genes (AVIL, PADI4, ARHGAP24, ST3GAL6, and BICDL2) as potential biomarkers. The cLBP diagnostic column chart model was established, demonstrating the accuracy of hub genes as biomarkers. A hub mRNA-related interaction network was constructed to identify potential therapeutic drugs, followed by verification of hub gene expression levels to validate their role in cLBP. Moreover, the investigation into immune cell infiltration revealed substantial disparities in the presence of five distinct immune cell types between the chronic LBP and acute LBP cohorts. Specifically, activated effector memory CD8 T cells (R = - 0.5407, p-value < 0.001) ,and CD56bright natural killer cells (R = - 0.5438, p-value < 0.001) were all found to be significantly different. These findings suggest that immune involvement may play a role in the development of cLBP. This study identified diagnostic biomarkers and therapeutic targets for cLBP, offering promising avenues for improved diagnosis and treatment. The identification of specific biomarkers, including AVIL, PADI4, ARHGAP24, ST3GAL6, and BICDL2, enhances diagnostic precision by enabling the stratification of cLBP subtypes based on underlying pathophysiology.", "claims": [{"id": "claim-method", "statement": "Statistical analysis was performed using R software, version 4.1.2. The Spearman correlation test was selected to ascertain the correlation between two variables. Comparisons between the two groups were made with the Wilcoxon test. Comparisons between three or more groups were made with the Kruskal–Wallis test. A two-tailed p-value of < 0.05 was indicative of statistical significance. The ‘pROC’ R package was used to create ROC curves and determine AUC values for the feature genes, thus assessing their potential as diagnostic indicators24.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40670404", "locator": "sections[11] \"Statistical analysis\" paragraph 2", "quote": "Statistical analysis was performed using R software, version 4.1.2."}, {"asset": "source:pmid:40670404", "locator": "sections[11] \"Statistical analysis\" paragraph 2", "quote": "The Spearman correlation test was selected to ascertain the correlation between two variables."}, {"asset": "source:pmid:40670404", "locator": "sections[11] \"Statistical analysis\" paragraph 2", "quote": "Comparisons between the two groups were made with the Wilcoxon test."}, {"asset": "source:pmid:40670404", "locator": "sections[11] \"Statistical analysis\" paragraph 2", "quote": "Comparisons between three or more groups were made with the Kruskal–Wallis test."}, {"asset": "source:pmid:40670404", "locator": "sections[11] \"Statistical analysis\" paragraph 2", "quote": "A two-tailed p-value of < 0.05 was indicative of statistical significance."}, {"asset": "source:pmid:40670404", "locator": "sections[8] \"Utilizing receiver operating characteristic curve analysis for evaluation\" paragraph 2", "quote": "The ‘pROC’ R package was used to create ROC curves and determine AUC values for the feature genes, thus assessing their potential as diagnostic indicators24."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The dataset(GSE177034) employed in this study are available via the GEO database (GeneExpressionOmnibus, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE177034). Genes related to pyroptosis were sourced from earlier investigations(10.1038/nri3452, 10.1038/s41420-021-00451-x, 10.1016/j.jsb.2017.08.001, 10.1038/s41568-019-0123-y, 10.1038/s41419-019-1883-8, 10.1111/imr.12296).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40670404", "locator": "sections[29] \"Data availability\" paragraph 2", "quote": "The dataset(GSE177034) employed in this study are available via the GEO database (GeneExpressionOmnibus, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE177034). Genes related to pyroptosis were sourced from earlier investigations(10.1038/nri3452, 10.1038/s41420-021-00451-x, 10.1016/j.jsb.2017.08.001, 10.1038/s41568-019-0123-y, 10.1038/s41419-019-1883-8, 10.1111/imr.12296)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Machine learning screening identified five pyroptosis-related hub genes—AVIL, PADI4, ARHGAP24, ST3GAL6, and BICDL2—as potential diagnostic biomarkers for chronic low back pain.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40670404", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Machine learning approaches identified five pyroptosis relate hub genes (AVIL, PADI4, ARHGAP24, ST3GAL6, and BICDL2) as potential biomarkers."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Machine learning screening identified five pyroptosis-related hub genes—AVIL, PADI4, ARHGAP24, ST3GAL6, and BICDL2—as potential diagnostic biomarkers for chronic low back pain.", "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:40670404"], "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:GSE177034"], "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:GSE177034"], "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:40670404", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1038/s41598-025-06756-6", "sha256": "sha256:312f02d4ad6f0189d3195ad788ded7ed08684b835c17ad0095940807d3c6bb80", "bytes": 56142, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1038/s41598-025-06756-6", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12267434", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE177034", "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=GSE177034", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE177034", "version": null, "note": "The dataset(GSE177034) employed in this study are available via the GEO database (GeneExpressionOmnibus, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE177034). Genes related to pyroptosis were sourced from earlier investigations(10.1038/nri3452, 10.1038/s41420-021-00451-x, 10.1016/j.jsb.2017.08.001, 10.1038/s41568-019-0123-y, 10.1038/s41419-019-1883-8, 10.1111/imr.12296).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The dataset(GSE177034) employed in this study are available via the GEO database (GeneExpressionOmnibus, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE177034). Genes related to pyroptosis were sourced from earlier investigations(10.1038/nri3452, 10.1038/s41420-021-00451-x, 10.1016/j.jsb.2017.08.001, 10.1038/s41568-019-0123-y, 10.1038/s41419-019-1883-8, 10.1111/imr.12296).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM5370696", "GSM5370697", "GSM5370698", "GSM5370699", "GSM5370700", "GSM5370701", "GSM5370702", "GSM5370703", "GSM5370704", "GSM5370705", "GSM5370706", "GSM5370707", "GSM5370708", "GSM5370709", "GSM5370710", "GSM5370711", "GSM5370712", "GSM5370713", "GSM5370714", "GSM5370715", "GSM5370716", "GSM5370717", "GSM5370718", "GSM5370719", "GSM5370720", "GSM5370721", "GSM5370722", "GSM5370723", "GSM5370724", "GSM5370725", "GSM5370726", "GSM5370727", "GSM5370728", "GSM5370729", "GSM5370730", "GSM5370731", "GSM5370732", "GSM5370733", "GSM5370734", "GSM5370735", "GSM5370736", "GSM5370737", "GSM5370738", "GSM5370739", "GSM5370740", "GSM5370741", "GSM5370742", "GSM5370743", "GSM5370744", "GSM5370745", "GSM5370746", "GSM5370747", "GSM5370748", "GSM5370749", "GSM5370750", "GSM5370751", "GSM5370752", "GSM5370753", "GSM5370754", "GSM5370755", "GSM5370756", "GSM5370757", "GSM5370758", "GSM5370759", "GSM5370760", "GSM5370761", "GSM5370762", "GSM5370763", "GSM5370764", "GSM5370765", "GSM5370766", "GSM5370767", "GSM5370768", "GSM5370769", "GSM5370770", "GSM5370771", "GSM5370772", "GSM5370773", "GSM5370774", "GSM5370775", "GSM5370776", "GSM5370777", "GSM5370778", "GSM5370779", "GSM5370780", "GSM5370781", "GSM5370782", "GSM5370783", "GSM5370784", "GSM5370785", "GSM5370786", "GSM5370787", "GSM5370788", "GSM5370789", "GSM5370790", "GSM5370791", "GSM5370792", "GSM5370793", "GSM5370794", "GSM5370795", "GSM5370796", "GSM5370797", "GSM5370798", "GSM5370799", "GSM5370800", "GSM5370801", "GSM5370802", "GSM5370803", "GSM5370804", "GSM5370805", "GSM5370806", "GSM5370807", "GSM5370808", "GSM5370809", "GSM5370810", "GSM5370811", "GSM5370812", "GSM5370813", "GSM5370814", "GSM5370815", "GSM5370816", "GSM5370817", "GSM5370818", "GSM5370819", "GSM5370820", "GSM5370821", "GSM5370822", "GSM5370823", "GSM5370824", "GSM5370825", "GSM5370826", "GSM5370827", "GSM5370828", "GSM5370829", "GSM5370830", "GSM5370831", "GSM5370832", "GSM5370833", "GSM5370834", "GSM5370835", "GSM5370836", "GSM5370837", "GSM5370838", "GSM5370839", "GSM5370840", "GSM5370841", "GSM5370842", "GSM5370843", "GSM5370844", "GSM5370845", "GSM5370846", "GSM5370847", "GSM5370848", "GSM5370849", "GSM5370850", "GSM5370851", "GSM5370852", "GSM5370853", "GSM5370854", "GSM5370855", "GSM5370856", "GSM5370857", "GSM5370858", "GSM5370859", "GSM5370860", "GSM5370861", "GSM5370862", "GSM5370863", "GSM5370864", "GSM5370865", "GSM5370866", "GSM5370867", "GSM5370868", "GSM5370869", "GSM5370870", "GSM5370871", "GSM5370872", "GSM5370873", "GSM5370874", "GSM5370875", "GSM5370876", "GSM5370877", "GSM5370878", "GSM5370879", "GSM5370880", "GSM5370881", "GSM5370882", "GSM5370883", "GSM5370884", "GSM5370885", "GSM5370886", "GSM5370887", "GSM5370888", "GSM5370889", "GSM5370890", "GSM5370891"], "sample_count": 196, "group_sizes": null, "group_sizes_basis": null, "platform": "11154", "taxon": "Homo sapiens", "title": "Acute Inflammatory Response via Neutrophil Activation Protects Against the Development of Chronic Pain", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE177034 not downloaded", "asset:data:geo:GSE177034 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "reordered", "quote": "Statistical analysis was performed using R software, version 4.1.2. 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