{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:26042604", "kind": "science-record", "revision": 7, "content_hash": "sha256:b470ae4e086e3e26b1f7a59642e5b488b16cd943586551981d6713c2110de372", "created_at": "2026-11-01T15:40:09Z", "updated_at": "2026-11-01T21:20:00Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Pathway-based gene signatures predicting clinical outcome of lung adenocarcinoma.", "doi": "10.1038/srep10979", "pmid": "26042604", "authors": ["Ya-Hsuan Chang", "Chung-Ming Chen", "Hsuan-Yu Chen", "Pan-Chyr Yang"], "journal": "Scientific reports", "year": 2015, "abstract": "Lung adenocarcinoma is often diagnosed at an advanced stage with poor prognosis. Patients with different clinical outcomes may have similar clinico-pathological characteristics. The results of previous studies for biomarkers for lung adenocarcinoma have generally been inconsistent and limited in clinical application. In this study, we used inverse-variance weighting to combine the hazard ratios for the four datasets and performed pathway analysis to identify prognosis-associated gene signatures. A total of 2,418 genes were found to be significantly associated with overall survival. Of these, a 21-gene signature in the HMGB1/RAGE signalling pathway and a 31-gene signature in the clathrin-coated vesicle cycle pathway were significantly associated with prognosis of lung adenocarcinoma across all four datasets (all p-values < 0.05, log-rank test). We combined the scores for the three pathways to derive a combined pathway-based risk (CPBR) score. Three pathway-based signatures and CPBR score also had more predictive power than single genes. Finally, the CPBR score was validated in two independent cohorts (GSE14814 and GSE13213 in the GEO database) and had significant adjusted hazard ratios 2.72 (p-value < 0.0001) and 1.71 (p-value < 0.0001), respectively. These results could provide a more complete picture of the lung cancer pathogenesis.", "claims": [{"id": "claim-method", "statement": "In order to determine whether genes were significantly associated with overall survival, multivariate Cox proportional hazards regression using the clinical covariates of age, sex and stage was performed on each of the 4 datasets. Each gene in a given dataset was assigned a hazard ratio (HR), and the corresponding p value was estimated by Cox regression analysis, giving 4 HR and 4 p values for each gene, then the inverse-variance weighting method was used to combine the HRs from the four datasets38. The gene expression and clinical data for these 4 groups were obtained from https://array.nci.nih.gov/caarray/project/details.action? project.id= 182.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:26042604", "locator": "sections[17] \"Identification of genes showing statistically significant differential expression using multivariate Cox proportional hazards regression\" paragraph 2", "quote": "In order to determine whether genes were significantly associated with overall survival, multivariate Cox proportional hazards regression using the clinical covariates of age, sex and stage was performed on each of the 4 datasets."}, {"asset": "source:pmid:26042604", "locator": "sections[17] \"Identification of genes showing statistically significant differential expression using multivariate Cox proportional hazards regression\" paragraph 2", "quote": "Each gene in a given dataset was assigned a hazard ratio (HR), and the corresponding p value was estimated by Cox regression analysis, giving 4 HR and 4 p values for each gene, then the inverse-variance weighting method was used to combine the HRs from the four datasets38."}, {"asset": "source:pmid:26042604", "locator": "sections[15] \"Study population and gene expression data\" paragraph 2", "quote": "The gene expression and clinical data for these 4 groups were obtained from https://array.nci.nih.gov/caarray/project/details.action? 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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}}}