{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39749345", "kind": "science-record", "revision": 3, "content_hash": "sha256:415ed979fc4401c58f7b4ba7f87c83c0012c06d7d3ce7bdbdc2448f65ffe390b", "created_at": "2026-11-01T20:30:05Z", "updated_at": "2026-11-01T22:13:29Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Exploration and validation of a novel reactive oxygen species-related signature for predicting the prognosis and chemotherapy response of patients with bladder cancer.", "doi": "10.3389/fimmu.2024.1493528", "pmid": "39749345", "authors": ["Yulei Li", "Lulu Zhang", "Gang Xu", "Gang Xu", "Jiajun Chen", "Keyuan Zhao", "Mengyao Li", "Jing Jin", "Chao Peng", "Kaifang Wang", "Shouhua Pan", "Ke Zhu"], "journal": "Frontiers in immunology", "year": 2024, "abstract": "Background: Reactive Oxygen Species (ROS), a hallmark of cancer, is related to prognosis, tumor progression, and treatment response. Nevertheless, the correlation of ROS-based molecular signature with clinical outcome and immune cell infiltration has not been thoroughly studied in bladder cancer (BLCA). Accordingly, we aimed to thoroughly examine the role and prognostic value of ROS-related genes in BLCA.\nMethods: We obtained RNA sequencing and clinical data from The Cancer Genome Atlas (TCGA) for bladder cancer (BLCA) patients and identified ROS-associated genes using the GeneCards and Molecular Signatures Database (MSigDB). We then analyzed differential gene expression between BLCA and normal tissues and explored the functions of these ROS-related genes through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI) analysis. Prognostic ROS-related genes were identified using Univariate Cox regression (UCR) and LASSO analyses, which were further refined in a Multivariate Cox Regression (MCR) analysis to develop a Prognostic Signature (PS). This PS was validated in the GSE13507 cohort, assessing its predictive power with Kaplan-Meier survival and time-dependent ROC curves. To forecast BLCA outcomes, we constructed a nomogram integrating the PS with clinical variables. We also investigated the signature's molecular characteristics through Gene Set Enrichment Analysis (GSEA), Immune Cell Infiltration (ICI), and Tumor Mutational Burden (TMB) analyses. The Genomics of Drug Sensitivity in Cancer (GDSC) database was used to predict chemotherapy responses based on the PS. Additionally, we screened for Small-Molecule Drugs (SMDs) targeting ROS-related genes using the CMAP database. Finally, we validated our findings by checking protein levels of the signature genes in the Human Protein Atlas (HPA) and confirmed the role of Aldo-keto reductase family 1 member B1 (AKR1B1) through in vitro experiments.\nResults: The constructed and validated PS that comprised 17 ROS-related genes exhibited good performance in predicting overall survival (OS), constituting an independent prognostic biomarker in BLCA patients. Additionally, we successfully established a nomogram with superior predictive capacity, as indicated by the calibration plots. The bioinformatics analysis findings showcased the implication of PS in several oncogenic pathways besides tumor ICI regulation. The PS was negatively associated with the TMB. The high-risk group patients had greater chemotherapy sensitivity in comparison to low-risk group patients. Further, 11 candidate SMDs were identified for treating BLCA. The majority of gene expression exhibited a correlation with the protein expression. In addition, the expression of most genes was consistent with protein expression. Furthermore, to test the gene reliability we constructed, AKR1B1, one of the seventeen genes identified, was used for in-depth validation. In vitro experiments indicate that siRNA-mediated AKR1B1 silencing impeded BLCA cell viability, migration, and proliferation.\nConclusions: We identified a PS based on 17 ROS-related genes that represented independent OS prognostic factors and 11 candidate SMDs for BLCA treatment, which may contribute to the development of effective individualized therapies for BLCA.", "claims": [{"id": "claim-method", "statement": "The prognosis-associated ROS-related genes were identified via Univariate Cox regression (UCR) analysis (survival package) and least absolute shrinkage and selection operator (LASSO) regression analysis (glmnet and survival package) with P < 0.05 in the TCGA dataset, followed by incorporating the results into the Multivariate Cox Regression (MCR) analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39749345", "locator": "sections[8] \"Construction and validation of the prognostic signature of ROS\" paragraph 2", "quote": "The prognosis-associated ROS-related genes were identified via Univariate Cox regression (UCR) analysis (survival package) and least absolute shrinkage and selection operator (LASSO) regression analysis (glmnet and survival package) with P < 0.05 in the TCGA dataset, followed by incorporating the results into the Multivariate Cox Regression (MCR) analysis."}], "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 authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39749345", "locator": "sections[38] \"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 authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A prognostic signature comprising 17 ROS-related genes was constructed and validated as an independent predictor of overall survival in bladder cancer patients.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39749345", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The constructed and validated PS that comprised 17 ROS-related genes exhibited good performance in predicting overall survival (OS), constituting an independent prognostic biomarker in BLCA patients."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A prognostic signature comprising 17 ROS-related genes was constructed and validated as an independent predictor of overall survival in bladder cancer patients.", "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:39749345"], "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:GSE13507"], "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:GSE13507"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39749345", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2024.1493528", "sha256": "sha256:ad23876f2478b582c08b14afe5aa63dac866bee358914aa344b8de22ea06d1f7", "bytes": 63471, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2024.1493528", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11693660", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE13507", "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=GSE13507", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE13507", "version": null, "note": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/ Supplementary Material . 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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": ["GSE13507"], "resolved_accessions": ["GSE13507"], "statements": ["The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors."], "basis": "The paper names GSE13507 in Gene Expression Omnibus and the accession resolves in the repository. 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Methods: We obtained RNA sequencing and clinical data from The Cancer Genome Atl", "trol tissues ( Figure 13 ). In line with the RNA sequencing data, P4BH, FASN, AKR1B1, and CBG5 proteins,"], "order_basis": "paper_text_order:553", "id": "assay:1"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["lidation. In vitro experiments indicate that siRNA-mediated AKR1B1 silencing impeded BLCA cell", "elsinki. Cell culture, treatments, and siRNA transfection Human BLCA cells (T24 and 5637) were procure", "e cell culture plate. After a 48-h period of transfection, the cells were gathered for additional asse", "n of Helsinki. Cell culture, treatments, and siRNA transfection Human BLCA cells (T24 and 5637)"], "order_basis": "paper_text_order:3122", "id": "assay:2"}, {"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": ["ollected from Shaoxing People’s Hospital for immunohistochemical staining (IHC) and western blot. No patient", "s Hospital for immunohistochemical staining (IHC) and western blot. No patient in this study", "ne genes in the Human Protein Atlas database IHC was utilized to additionally investigate the"], "order_basis": "paper_text_order:4067", "id": "assay:3"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["l for immunohistochemical staining (IHC) and western blot. No patient in this study had received radia"], "order_basis": "paper_text_order:4106", "id": "assay:4"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["e control (NC), and siAKR1B1 groups. The two cell lines were cultured in MCCOY’S 5A (Gibco, USA) and 1640 (Gibco,", "and siAKR1B1 groups. The two cell lines were cultured in MCCOY’S 5A (Gibco, USA) and 1640 (Gibco, USA"], "order_basis": "paper_text_order:4868", "id": "assay:5"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The prognosis-associated ROS-related genes were identified via Univariate Cox regression (UCR) analysis (survival package) and least absolute shrinkage and selection operator (LASSO) regression analysis (glmnet and survival package) with P < 0.05 in the TCGA dataset, followed by incorporating the results into the Multivariate Cox Regression (MCR) analysis."], "order_basis": "consumes_earlier_output", "id": "assay:6"}]},"meta":{"api_version":"v1","automation_ladder_snapshot":"ba34b49490d9bfaf","automation_ladder_caveats":["Method extraction is rule-based and has no hand-judged accuracy sample. 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Timing awaits the first executed replication.","4,407 of 5,529 records (79.7%) model to 0.00 hours because no assay was matched, which the ranking then reads as \"cheapest\".","0 of 10 shortlisted records carry a 0.00-hour estimate."],"claim":"Estimated replication runtime","gloss":"The hour figures are estimates built from assay mentions; timing awaits the first executed replication.","detail":"The hour figures are a cost model derived from the bench steps implied by each matched assay family. The first executed replication will supply measured timing. Records without an assay match currently receive a zero-hour model value.","status":"unverified","severity":"high"},{"code":"signal_score_without_citations","basis":["5,529 of 5,529 records (100.0%) have no citation count from the source metadata."],"claim":"Signal score","gloss":"The signal score uses publication-type weight because the mirror supplied zero citation counts.","detail":"The source supplied no citation counts for any record in this run, so the signal score is publication-type weight only. The citation term of the ranking is inert here, and the shortlist is ordered by publication type alone.","status":"unverified","severity":"high"},{"code":"abstract_absent","basis":["1,667 of 5,529 records (30.2%) carry no abstract at all."],"claim":"Evidence base for classification","gloss":"Some records contain a title and publication type only, defining the available classification evidence.","detail":"Where the mirror contains a title and publication types only, those fields define the classifier evidence. A methods section is required for fuller automated and human review.","status":"unverified","severity":"medium"},{"code":"classifier_agreement_measured","basis":["Published two-way decision agreement 77.7% (310 of 399 decidable records) from a stratified hand-check of 438 real records.","Three-way diagnostic agreement 73.9% (288 of 390 decidable records).","data_only agreement 75.2% (100 of 133 decidable).","48 record(s) could not be decided from title and abstract and were excluded from the denominator.","56 analysis-only records were published under another work type, so the data_only share is not an upper bound."],"claim":"Published automatable decision","gloss":"This figure has been checked against a human reading the same papers, so we know how often it is right.","detail":"The published automatable / not-automatable distribution comes from a rule-based classifier that was hand-checked against a fixed ground-truth definition. The agreement rates below are measured, not estimated. The three-way work type remains a diagnostic and is reported separately.","status":"measured","severity":"high"},{"code":"llm_comparison_not_measured","basis":["rule_based_v1+lex99e1195c7d6f produced 5,529 of 5,529 classifications.","Measured on 438 labelled records; these are RULE-BASED figures, not model results."],"claim":"Rule-based versus LLM agreement","gloss":"Every number here is the rule engine’s own. Model comparison begins when a working API credential is connected and measured.","detail":"The published two-way decision agreed with a human reading on 310 of 399 decidable records (77.7%). The diagnostic three-way label agreed on 288 of 390 decidable records (73.9%). Every percentage in this run belongs to the rule engine. Model comparison begins when a working API credential is connected and measured.","status":"not_measured","severity":"high"},{"code":"confidence_is_a_band","basis":["low band: 135 of 210 hand-judged records were correct, 64.3% [57.6, 70.5] (95% CI).","medium band: 80 of 104 hand-judged records were correct, 76.9% [68.0, 84.0] (95% CI).","high band: 73 of 76 hand-judged records were correct, 96.0% [89.0, 98.7] (95% CI).","A fitted calibrated probability was built, measured and withdrawn: it overstated held-out accuracy and reorders nothing."],"claim":"Confidence band and evidence score","gloss":"The confidence band carries a measured accuracy interval; 0.85 represents relative rank strength.","detail":"Confidence on this run is a BAND plus its measured accuracy interval. The number stored alongside each record is a monotone evidence score that orders records; 0.85 represents relative rank strength. A fitted probability was withdrawn after it overstated held-out accuracy. Threshold on the band.","status":"measured","severity":"medium"},{"code":"three_way_split_is_diagnostic","basis":["The corpus is published at the two-way decision: automatable or not-automatable. The three-way split (data_only / physical / mixed) is published as a diagnostic with its measured reliability attached, not as a claim, because the rule engine's `mixed` call cannot be defended.","The engine called 22 record(s) mixed; 10 matched the human judgement (45.5%, 95% CI 26.9-65.3).","The engine's `mixed` call is right on 10/22 hand-judged records (45.5%, 95% CI 26.9%-65.3%); a constant `physical` guess scores 36.4%.","The engine's `mixed` call does not reliably beat a constant `physical` guess on the hand-judged records it labels mixed.","The sign of that difference flips between two independent samples, so the three-way refinement is not demonstrably informative.","The mixed stratum contributes a disproportionate share of errors relative to its size.","At title-only depth the physical/mixed split collapses: a title says that work was done, not whether it was also analysed."],"claim":"The published decision is two-way","gloss":"The three-way split is shown for diagnosis only. The published split is two ways.","detail":"Count and filter the corpus on automatable versus not-automatable. The data_only / physical / mixed split remains an internal engine diagnostic because the mixed call has lower measured reliability.","status":"measured","severity":"medium"},{"code":"automatable_flag_unproven","basis":["6 of 29 assay families are marked automatable now: meta_analysis, machine_learning, survival_analysis, pca, molecular_docking, differential_expression.","The flag is a rule over assay family and work type; validation begins with the first executed replication.","It inherits the 75.2% data_only agreement rate, because the flag requires the record to be analysis-only."],"claim":"Automatable now","gloss":"This flag marks assay families the rules classify as data-only. The first executed replication will validate it.","detail":"This flag marks families the rules consider replicable from data alone. Its validity depends on the analysis-only classification and will be measured through an executed replication.","status":"unverified","severity":"medium"}],"confidence_policy":"band_with_measured_interval","confidence_contract":{"policy":"band_with_measured_interval","summary":"Confidence is reported as a BAND with a measured accuracy interval. The raw evidence score supplies monotone ordering. A fitted point estimate was withdrawn after it overstated held-out accuracy.","evidence_score":"A monotone evidence score in [0,1] built from cue mass, axis separation and text coverage. Use it to order records. Interpret 0.85 as relative rank strength.","confidence_band":"low | medium | high. Consumers threshold on this value.","band_accuracy":"Wilson 95% interval on the measured agreement of the hand-judged records in this band.","calibrated_confidence":"WITHDRAWN. Reintroduction requires held-out evidence demonstrating reliable estimates across every bin."},"band_accuracy":{"low":{"n":210,"low":0.576,"band":"low","high":0.7046,"agree":135,"accuracy":0.6429},"high":{"n":76,"low":0.8903,"band":"high","high":0.9865,"agree":73,"accuracy":0.9605},"medium":{"n":104,"low":0.6795,"band":"medium","high":0.8397,"agree":80,"accuracy":0.7692}},"provider":"rule_based_v1+lex99e1195c7d6f","lexicon_id":"99e1195c7d6f","contract_published_at":"2026-10-23T12:25:29.022232+00:00","confidence_is_band":true,"confidence_is_probability":false,"decision_taxonomy":"two_way","decidable_fraction_two_way":0.8854,"decidable_fraction_two_way_low":0.8565,"decidable_fraction_two_way_high":0.9143,"decidable_fraction_three_way":0.8586,"decidable_fraction_three_way_low":0.8287,"decidable_fraction_three_way_high":0.8884,"decidable_population":5529,"validation_sample_size":438,"three_way_cost_fraction":0.0268,"three_way_cost_records":148,"decision_counts":{"automatable":230,"not_automatable":5299},"decision_split":{"automatable":{"count":230,"share":0.04159884246699222},"not_automatable":{"count":5299,"share":0.9584011575330078}},"diagnostic_work_type_counts":{"mixed":24,"physical":5275,"data_only":230}}}