{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37980291", "kind": "science-record", "revision": 3, "content_hash": "sha256:8add6944b69a7f36dab77f97d55fe56327d741d5d0df207c8fbdd772a6e56136", "created_at": "2026-11-01T19:02:53Z", "updated_at": "2026-11-01T22:10:41Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Novel diagnostic biomarkers of oxidative stress, immune- infiltration characteristics and experimental validation of SERPINE1 in colon cancer.", "doi": "10.1007/s12672-023-00833-w", "pmid": "37980291", "authors": ["Kaisheng Yuan", "Di Hu", "Xiaocong Mo", "Ruiqi Zeng", "Bing Wu", "Zunhao Zhang", "Ruixiang Hu", "Cunchuan Wang"], "journal": "Discover oncology", "year": 2023, "abstract": "BACKGROUND: Colon cancer (CC) is a prevalent malignant tumor that affects the colon in the gastrointestinal tract. Its aggressive nature, strong invasiveness, and rapid progression make it a significant health concern. In addition, oxidative stress can lead to the production of reactive oxygen species (ROS) that surpass the body's antioxidant defense capacity, causing damage to proteins, lipids, and DNA, potentially promoting tumor development. However, the relationship between CC and oxidative stress requires further investigation.\nMETHODS: We collected gene expression data and clinical data from 473 CC patients from The Cancer Genome Atlas (TCGA) dataset. Additionally, we obtained 433 oxidative stress genes from Genecards ( https://www.genecards.org/ ). Using univariate, multivariate, and LASSO Cox regression analyses, we developed predictive models for oxidative stress-related genes in CC patients. To validate the models, we utilized data from the Gene Expression Omnibus (GEO) database. We assessed the accuracy of the models through various techniques, including the creation of a nomogram, receiver operating characteristic curve (ROC) analysis, and principal component analysis (PCA). The Cytoscape program was utilized to identify hub genes among differentially expressed genes (DEGs) in tumor patients using the TCGA dataset. Subsequently, we conducted survival analysis, clinical relevance analysis, and immune cell relevance analysis for the intersected genes obtained by combining the hub genes with the genes from the predictive models. Moreover, we investigated the mRNA expression and potential functions of these intersected genes using a range of experimental approaches.\nRESULTS: In both the TCGA and GSE17538 datasets, patients classified as high-risk had significantly shorter overall survival compared to those in the low-risk group (TCGA: p < 0.001; GSE17538: p = 0.010). As a result, we decided to further investigate the role of SERPINE1. Our survival analysis revealed that patients with high expression of SERPINE1 had a significantly lower probability of survival compared to those with low expression (p < 0.05). Additionally, our clinical correlation analysis showed a significant relationship between SERPINE1 expression and T, N, and M stages, as well as tumor grade. Furthermore, our immune infiltration correlation analysis demonstrated notable differences in multiple immune cells between the high- and low-expression groups of SERPINE1. To validate our findings, we conducted experimental tests and observed that knocking down SERPINE1 in colon cancer cells resulted in significant reductions in cell viability and proliferation. Interestingly, we also noticed an increase in oxidative stress parameters, such as ROS and MDA levels, while the levels of reduced GSH decreased upon SERPINE1 knockdown. These findings suggest that the antineoplastic effect of silencing SERPINE1 may be associated with the induction of oxidative stress.\nCONCLUSION: In conclusion, this study introduces a new approach for the early diagnosis and treatment of CC, and further exploration of SERPINE1 could potentially lead to a significant advancement.", "claims": [{"id": "claim-method", "statement": "Using univariate, multivariate, and LASSO Cox regression analyses, we developed predictive models for oxidative stress-related genes in CC patients.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37980291", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Using univariate, multivariate, and LASSO Cox regression analyses, we developed predictive models for oxidative stress-related genes in CC patients."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw transcriptome data of this study are available in the TCGA database (TCGA cohorts) (https://portal.gdc.cancer.gov/) and the GEO database (GSE17538) (https://www.ncbi.nlm.nih.gov/gds/). Oxidative stress genes were downloaded and collated from Genecards (https://www.genecards.org/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37980291", "locator": "sections[41] \"Data availability\" paragraph 2", "quote": "The raw transcriptome data of this study are available in the TCGA database (TCGA cohorts) (https://portal.gdc.cancer.gov/) and the GEO database (GSE17538) (https://www.ncbi.nlm.nih.gov/gds/). Oxidative stress genes were downloaded and collated from Genecards (https://www.genecards.org/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Through LASSO regression analysis, we identified 16 genes (NGF, IL13, RPS6KA5, TERT, CDKN2A, SERPINE1, CD36, PPARGC1A, ACADL, ACOX1, POMC, BDNF, MSRA, DDIT3, GSTM1, CPT2) based on the best λ value to construct a prognostic model (Supplementary Figure S4A–B).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37980291", "locator": "sections[26] \"Construction and evaluation of a prognostic model for CC based on oxidative stress-related genes\" paragraph 2", "quote": "Through LASSO regression analysis, we identified 16 genes (NGF, IL13, RPS6KA5, TERT, CDKN2A, SERPINE1, CD36, PPARGC1A, ACADL, ACOX1, POMC, BDNF, MSRA, DDIT3, GSTM1, CPT2) based on the best λ value to construct a prognostic model (Supplementary Figure S4A–B)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Through LASSO regression analysis, we identified 16 genes (NGF, IL13, RPS6KA5, TERT, CDKN2A, SERPINE1, CD36, PPARGC1A, ACADL, ACOX1, POMC, BDNF, MSRA, DDIT3, GSTM1, CPT2) based on the best λ value to construct a prognostic model (Supplementary Figure S4A–B).", "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:37980291"], "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:GSE17538"], "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:GSE17538"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37980291", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1007/s12672-023-00833-w", "sha256": "sha256:6f696a5fbe24ffc37907f437d921cec06afbf5b7d6ba61e2fd4294f6140b687d", "bytes": 64529, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1007/s12672-023-00833-w", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10657345", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE17538", "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=GSE17538", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE17538", "version": null, "note": "The raw transcriptome data of this study are available in the TCGA database (TCGA cohorts) (https://portal.gdc.cancer.gov/) and the GEO database (GSE17538) (https://www.ncbi.nlm.nih.gov/gds/). 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These findings suggest that the antineoplas"], "order_basis": "paper_text_order:2936", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["ned from Dr. Yunlong Chen. The CC cells were cultured in DMEN medium (Gibco). From August 2021 to Oct"], "order_basis": "paper_text_order:5621", "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": ["truction of the prognostic model for CC. D–E Immunohistochemical staining of SERPINE1 gene in normal tissue (", "KB)—Figure S9: (A-B) Three other samples of immunohistochemical analysis of SERPINE1 expression in CC patien", "PA, https://www.proteinatlas.org/) offers an IHC-based assay for relative protein abundance ["], "order_basis": "paper_text_order:9786", "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": ["itional file10 (PDF 164 KB)—Figure S10: Full western blot images. Additional file11 (XLS 10 KB)—Table"], "order_basis": "paper_text_order:17507", "id": "assay:4"}, {"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": ["Using univariate, multivariate, and LASSO Cox regression analyses, we developed predictive models for oxidative stress-related genes in CC patients."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]},"meta":{"api_version":"v1","automation_ladder_snapshot":"ba34b49490d9bfaf","automation_ladder_caveats":["Method extraction is rule-based and has no hand-judged accuracy sample. Evidence bands order textual support; method agreement intervals are null (n=0), never probabilities. Work-type validation does not validate methods.","Operation coverage describes only explicitly named methods. 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Resolving one blocker can leave another at the same tier."],"engine":"corpus_engine","engine_provider":"rule_based_v1+lex99e1195c7d6f","run_id":"run-20261023T122449232913","source":"esearch","source_detail":"PubMed mirror biomed_pubmed (read-only)","run_status":"complete","imported_at":"2026-11-03T20:16:52+00:00","generated_at":"2026-11-04T00:42:31+00:00","total_papers":5529,"total_assays_tracked":29,"automatable_assay_families":6,"validated":true,"caveat_count":9,"blocking_caveats":5,"caveats":[{"code":"low_evidence_dominates","basis":["4,152 of 5,529 classifications (75.1%) matched no cue evidence and sit at the 0.05 floor.","34 of 230 data_only calls (14.8%) are in that group."],"claim":"Work type and confidence bands","gloss":"Most records were classified from their title and framing alone, with assay-cue coverage at zero.","detail":"Most classifications in this run rest on no matched evidence at all. At the evidence floor the work type comes from title framing and a fixed prior, not from anything in the paper, so the published work-type split should be read as a rough triage signal rather than a measured distribution. The impact is bounded but not removed: since 2026-10-23 the engine excludes floor-confidence records from the shortlist entirely and publishes them separately as held out, so the recommendation is unaffected even though the census is.","status":"unverified","severity":"high"},{"code":"runtime_is_modelled","basis":["Runtime is summed from published per-assay hour figures. 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}}}