{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38186574", "kind": "science-record", "revision": 3, "content_hash": "sha256:91170a4513f77f9a09fee6aba06994d81ef19fcbc0ede2097f49262270e9a2ac", "created_at": "2026-11-01T19:20:06Z", "updated_at": "2026-11-01T22:10:59Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Leveraging diverse cell-death patterns to predict the clinical outcome of immune checkpoint therapy in lung adenocarcinoma: Based on muti-omics analysis and vitro assay.", "doi": "10.32604/or.2023.031134", "pmid": "38186574", "authors": ["Hongyuan Liang", "Yanqiu Li", "Yonggang Qu", "Lingyun Zhang"], "journal": "Oncology research", "year": 2023, "abstract": "Advanced LUAD shows limited response to treatment including immune therapy. With the development of sequencing omics, it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response markers. Using GSE72094 (n = 386) and GSE31210 (n = 226) gene expression profile data in the GEO database, we identified genes associated with lung adenocarcinoma (LUAD) death using tools such as \"edgeR\" and \"maftools\" and visualized the characteristics of these genes using the \"circlize\" R package. We constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression methods. By calculating the cell death index (CDI) of each individual, we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis (PCA) and Kaplan-Meier analysis. We also used the \"ConsensusClusterPlus\" tool for unsupervised clustering of LUAD subtypes based on model genes. In addition, we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment analyses. We also used the TIDE algorithm to predict immunotherapy responses in the CDI cohort. Finally, we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture experiments. The study utilized the TCGA-LUAD cohort (n = 493) and identified 2,901 genes that are differentially expressed in patients with LUAD. Through KEGG and GO enrichment analysis, these genes were found to be involved in a wide range of biological pathways. The study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk scores. By comparing the overall survival (OS) outcomes of patients with different CDI values, it was found that increased CDI levels were significantly associated with lower OS rates. In addition, the study used unsupervised cluster analysis to divide 115 LUAD patients into two distinct clusters with significant differences in OS timing. Finally, a prognostic indicator called CDI was established and its feasibility as an independent prognostic indicator was evaluated by Cox proportional risk regression analysis. The immunotherapy efficacy was more sensitive in the group with high expression of programmed cell death models. Relationship between programmed cell death (PCD) signature models and drug reactivity. After evaluating the median inhibitory concentration (IC50) of various drugs in LUAD samples, statistically significant differences in IC50 values were found in cohorts with high and low CDI status. Specifically, Gefitinib and Lapatinib had higher IC50 values in the high-CDI cohort, while Olaparib, Oxaliplatin, SB216763, and Axitinib had lower values. These results suggest that individuals with high CDI levels are sensitive to tyrosine kinase inhibitors and may be resistant to conventional chemotherapy. Therefore, this study constructed a gene model that can evaluate patient immunotherapy by using programmed cell death-related genes based on muti-omics. The CDI index composed of these programmed cell death-related genes reveals the heterogeneity of lung adenocarcinoma tumors and serves as a prognostic indicator for patients.", "claims": [{"id": "claim-method", "statement": "In order to assess the feasibility of CDI as an autonomous prognostic indicator, comprehensive univariate and multivariate Cox proportional hazards regression analyses were conducted.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38186574", "locator": "sections[19] \"Establishment and assessment of the nomogram survival model\" paragraph 2", "quote": "In order to assess the feasibility of CDI as an autonomous prognostic indicator, comprehensive univariate and multivariate Cox proportional hazards regression analyses were conducted."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analyzed for this study can be found in the GEO website (https://www.ncbi.nlm.nih.gov/geo/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38186574", "locator": "sections[28] \"Availability of Data and Materials\" paragraph 2", "quote": "The datasets analyzed for this study can be found in the GEO website (https://www.ncbi.nlm.nih.gov/geo/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Higher cell death index (CDI) was independently associated with poorer survival in patients with LUAD (multivariate HR = 3.49, 95% CI: 2.53–4.83, p < 0.001).", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "Further, after controlling for other covariates, the consequences of the multivariate analysis substantiated the significance of CDI as a self-reliant prognostic determinant in patients with LUAD (HR = 3.49, 95% CI: 2.53–4.83, p < 0.001, as shown in Fig. 6B)."}, "evidence": [{"asset": "source:pmid:38186574", "locator": "sections[19] \"Establishment and assessment of the nomogram survival model\" paragraph 2", "quote": "Further, after controlling for other covariates, the consequences of the multivariate analysis substantiated the significance of CDI as a self-reliant prognostic determinant in patients with LUAD (HR = 3.49, 95% CI: 2.53–4.83, p < 0.001, as shown in Fig. 6B)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Higher cell death index (CDI) was independently associated with poorer survival in patients with LUAD (multivariate HR = 3.49, 95% CI: 2.53–4.83, p < 0.001).", "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:38186574"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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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. It does not prove a complete protocol, compatible parameters, successful compilation or re-execution. Unrecognised or ambiguous methods require review.","Data reachability is a textual accession or public-data statement. No dataset was downloaded or checked for access, completeness or licence.","Capabilities are planning states seeded from the dated equipment register. No bench ownership, completed quote or partner booking is inferred. Procurement counts are dependencies, not guaranteed replications or financial returns.","Tier and blocker counts are deterministic assessments of this corpus, not measured agreement. R3 is reserved for procurement; unresolved methods and data require human work (R4). The most restrictive axis wins, with capability, method, data as tie-breaks. 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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. 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