Identification and validation of molecular subtypes' characteristics in bladder urothelial carcinoma based on autophagy-dependent ferroptosis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37920516", "kind": "science-record", "revision": 3, "content_hash": "sha256:6a4816ec0347635dc04c602faeaf3bc4c6d5ba80a44216b79f11ece70c3514ae", "created_at": "2026-11-01T19:02:48Z", "updated_at": "2026-11-01T22:10:34Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and validation of molecular subtypes' characteristics in bladder urothelial carcinoma based on autophagy-dependent ferroptosis.", "doi": "10.1016/j.heliyon.2023.e21092", "pmid": "37920516", "authors": ["Shiwei Liu", "Jing Zhai", "Deng Li", "Yu Peng", "Yi Wang", "Bo Dai"], "journal": "Heliyon", "year": 2023, "abstract": "Background: Nowadays, more evidences indicated that autophagy-dependent ferroptosis regulatory molecules (ADFRMs) may be closely related to various tumors. In current study, we intended to establish a prognostic ADFRMs signature and investigated its potential roles in bladder urothelial carcinoma (BLCA).\nMethods: Two distinct clusters were determined by consensus clustering with expression of 119 identified ADFRMs in BLCA. The tumor microenvironment was investigated through \"CIBERSORT\" algorithm, and enrichment analyses were utilized to seek molecular characteristics of differentially expressed genes (DEGs) between clusters. Moreover, a 2-ADFRMs prognostic signature including TRIB3 and WIPI1 was identified in TCGA cohort and further evaluated in the GSE13507 cohort. The qRT-PCR was conducted to examine the expression of prognostic genes. Further, the risk score was gained through calculating the level of TRIB3 and WIPI1 expression through the coefficient. The correlations between risk score with clinicopathologica features, tumor microenvironment, and drug sensitivity were explored.\nResults: Patients in TCGA-BLCA were grouped into two clusters with different expression patterns of ADFRMs. And the overall survival, tumor microenvironment and biological functions were significant different between two clusters. Moreover, a 2-ADFRMs model was constructed, and patients were separated into a low-risk and high-risk group. Survival analysis indicated patients with low risk promised a good prognosis, suggesting the risk score determined with ADFRMs signature exhibited an acceptable capacity for survival prediction in BLCA. Correlation analysis demonstrated risk score had close ties with age, stage, and tumor microenvironment. In vivo, the expression of prognostic genes was identified to be up-regulated in BLCA cell line T24.\nConclusion: The constructed 2-ADFRMs signature was a promising model to predict prognosis and correlated with tumor microenvironment, which had latent clinical value in the intervention for BLCA.", "claims": [{"id": "claim-method", "statement": "Through the Univariate Cox regression algorithm, three genes of 119 ADFRMs were identified as independent factors to predict prognosis which were further utilized to establish the ADFRMs signature in BLCA.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37920516", "locator": "sections[6] \"Establishment and validation of a prognostic model\" paragraph 2", "quote": "Through the Univariate Cox regression algorithm, three genes of 119 ADFRMs were identified as independent factors to predict prognosis which were further utilized to establish the ADFRMs signature in BLCA."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The total RNA-seq and the clinical data of TCGA-BLCA dataset and GSE13507 dataset acquired from TCGA database (http://cancergenome.nih.gov/) and GEO (https://www.ncbi.nlm.nih.gov/geo/) respectively. The “ADFRMs” set was identified from two online databases, including the “HAMdb” (hamdb.scbdd.com/home/index/) and the “FerrDb” (www.zhounan.org/ferrdb/current/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37920516", "locator": "sections[23] \"Data availability statement\" paragraph 2", "quote": "The total RNA-seq and the clinical data of TCGA-BLCA dataset and GSE13507 dataset acquired from TCGA database (http://cancergenome.nih.gov/) and GEO (https://www.ncbi.nlm.nih.gov/geo/) respectively. The “ADFRMs” set was identified from two online databases, including the “HAMdb” (hamdb.scbdd.com/home/index/) and the “FerrDb” (www.zhounan.org/ferrdb/current/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The scatter chart showed BLCA patients with a low risk score had a better prognosis (Fig. 5F).", "kind": "quantitative", "target": {"value": 0.003, "unit": "p-value", "tolerance": null, "source": "Besides, the survival analysis presented a similar result (Fig. 5G, p = 0.003)."}, "evidence": [{"asset": "source:pmid:37920516", "locator": "sections[15] \"Construction of a prognostic model with ADFRMs\" paragraph 2", "quote": "The scatter chart showed BLCA patients with a low risk score had a better prognosis (Fig. 5F)."}, {"asset": "source:pmid:37920516", "locator": "sections[15] \"Construction of a prognostic model with ADFRMs\" paragraph 2", "quote": "Besides, the survival analysis presented a similar result (Fig. 5G, p = 0.003)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The scatter chart showed BLCA patients with a low risk score had a better prognosis (Fig. 5F).", "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:37920516"], "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:37920516", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.heliyon.2023.e21092", "sha256": "sha256:8fa5a4d16b3f4fade1edc9c0893f86a2156e865ab73b66e361896f1750203d5b", "bytes": 46430, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1016/j.heliyon.2023.e21092", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10618552", "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 total RNA-seq and the clinical data of TCGA-BLCA dataset and GSE13507 dataset acquired from TCGA database (http://cancergenome.nih.gov/) and GEO (https://www.ncbi.nlm.nih.gov/geo/) respectively. The “ADFRMs” set was identified from two online databases, including the “HAMdb” (hamdb.scbdd.com/home/index/) and the “FerrDb” (www.zhounan.org/ferrdb/current/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The total RNA-seq and the clinical data of TCGA-BLCA dataset and GSE13507 dataset acquired from TCGA database (http://cancergenome.nih.gov/) and GEO (https://www.ncbi.nlm.nih.gov/geo/) respectively. The “ADFRMs” set was identified from two online databases, including the “HAMdb” (hamdb.scbdd.com/home/index/) and the “FerrDb” (www.zhounan.org/ferrdb/current/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM340537", "GSM340538", "GSM340539", "GSM340540", "GSM340541", "GSM340542", "GSM340543", "GSM340544", "GSM340545", "GSM340546", "GSM340547", "GSM340548", "GSM340549", "GSM340550", "GSM340551", "GSM340552", "GSM340553", "GSM340554", "GSM340555", "GSM340556", "GSM340557", "GSM340558", "GSM340559", "GSM340560", "GSM340561", "GSM340562", "GSM340563", "GSM340564", "GSM340565", "GSM340566", "GSM340567", "GSM340568", "GSM340569", "GSM340570", "GSM340571", "GSM340572", "GSM340573", "GSM340574", "GSM340575", "GSM340576", "GSM340577", "GSM340578", "GSM340579", "GSM340580", "GSM340581", "GSM340582", "GSM340583", "GSM340584", "GSM340585", "GSM340586", "GSM340587", "GSM340588", "GSM340589", "GSM340590", "GSM340591", "GSM340592", "GSM340593", "GSM340594", "GSM340595", "GSM340596", "GSM340597", "GSM340598", "GSM340599", "GSM340600", "GSM340601", "GSM340602", "GSM340603", "GSM340604", "GSM340605", "GSM340606", "GSM340607", "GSM340608", "GSM340609", "GSM340610", "GSM340611", "GSM340612", "GSM340613", "GSM340614", "GSM340615", "GSM340616", "GSM340617", "GSM340618", "GSM340619", "GSM340620", "GSM340621", "GSM340622", "GSM340623", "GSM340624", "GSM340625", "GSM340626", "GSM340627", "GSM340628", "GSM340629", "GSM340630", "GSM340631", "GSM340632", "GSM340633", "GSM340634", "GSM340635", "GSM340636", "GSM340637", "GSM340638", "GSM340639", "GSM340640", "GSM340641", "GSM340642", "GSM340643", "GSM340644", "GSM340645", "GSM340646", "GSM340647", "GSM340648", "GSM340649", "GSM340650", "GSM340651", "GSM340652", "GSM340653", "GSM340654", "GSM340655", "GSM340656", "GSM340657", "GSM340658", "GSM340659", "GSM340660", "GSM340661", "GSM340662", "GSM340663", "GSM340664", "GSM340665", "GSM340666", "GSM340667", "GSM340668", "GSM340669", "GSM340670", "GSM340671", "GSM340672", "GSM340673", "GSM340674", "GSM340675", "GSM340676", "GSM340677", "GSM340678", "GSM340679", "GSM340680", "GSM340681", "GSM340682", "GSM340683", "GSM340684", "GSM340685", "GSM340686", "GSM340687", "GSM340688", "GSM340689", "GSM340690", "GSM340691", "GSM340692", "GSM340693", "GSM340694", "GSM340695", "GSM340696", "GSM340697", "GSM340698", "GSM340699", "GSM340700", "GSM340701", "GSM340702", "GSM340703", "GSM340704", "GSM340705", "GSM340706", "GSM340707", "GSM340708", "GSM340709", "GSM340710", "GSM340711", "GSM340712", "GSM340713", "GSM340714", "GSM340715", "GSM340716", "GSM340717", "GSM340718", "GSM340719", "GSM340720", "GSM340721", "GSM340722", "GSM340723", "GSM340724", "GSM340725", "GSM340726", "GSM340727", "GSM340728", "GSM340729", "GSM340730", "GSM340731", "GSM340732", "GSM340733", "GSM340734", "GSM340735", "GSM340736", "GSM340737", "GSM340738", "GSM340739", "GSM340740", "GSM340741", "GSM340742", "GSM340743", "GSM340744", "GSM340745", "GSM340746", "GSM340747", "GSM340748", "GSM340749", "GSM340750", "GSM340751", "GSM340752", "GSM340753", "GSM340754", "GSM340755", "GSM340756", "GSM340757", "GSM340758", "GSM340759", "GSM340760", "GSM340761", "GSM340762", "GSM340763", "GSM340764", "GSM340765", "GSM340766", "GSM340767", "GSM340768", "GSM340769", "GSM340770", "GSM340771", "GSM340772", "GSM340773", "GSM340774", "GSM340775", "GSM340776", "GSM340777", "GSM340778", "GSM340779", "GSM340780", "GSM340781", "GSM340782", "GSM340783", "GSM340784", "GSM340785", "GSM340786", "GSM340787", "GSM340788", "GSM340789", "GSM340790", "GSM340791", "GSM340792"], "sample_count": 256, "group_sizes": null, "group_sizes_basis": null, "platform": "6102", "taxon": "Homo sapiens", "title": "Predective Value of Prognosis-Related Gene Expression Study in Primary Bladder Cancer", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE13507 not downloaded", "asset:data:geo:GSE13507 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Through the Univariate Cox regression algorithm, three genes of 119 ADFRMs were identified as independent factors to predict prognosis which were further utilized to establish the ADFRMs signature in BLCA."}}, {"id": "method-2", "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": 0.8, "band": "high", "quote": "Wilcoxon"}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "cox_ph", "expected_value": 0.003, "unit": "p-value", "tolerance": null, "state": "complete", "note": "The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold."}], "gaps": ["method.reader_differs_from_extractor"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["cox_ph"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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 total RNA-seq and the clinical data of TCGA-BLCA dataset and GSE13507 dataset acquired from TCGA database (http://cancergenome.nih.gov/) and GEO (https://www.ncbi.nlm.nih.gov/geo/) respectively. The “ADFRMs” set was identified from two online databases, including the “HAMdb” (hamdb.scbdd.com/home/index/) and the “FerrDb” (www.zhounan.org/ferrdb/current/)."], "basis": "The paper names GSE13507 in GEO database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:37920516", "data:geo:GSE13507"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE13507"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:58:05Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 13571, "completion_tokens": 2158, "cached_tokens": 264}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:37920516", "type": "paper", "label": "pmid:37920516"}, {"id": "source:pmid:37920516", "type": "manuscript", "label": "PMID 37920516 full text"}, {"id": "data:geo:GSE13507", "type": "dataset", "label": "GEO GSE13507"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37920516", "type": "paper", "label": "pmid:37920516"}, {"id": "source:pmid:37920516", "type": "manuscript", "label": "PMID 37920516 full text"}, {"id": "data:geo:GSE13507", "type": "dataset", "label": "GEO GSE13507"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37920516", "type": "extraction", "used": ["source:pmid:37920516"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE13507", "type": "accession_resolution", "used": ["data:geo:GSE13507"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:37920516", "parent_hash": "sha256:7208dee5108b23ef79834c9a9155fc6a60c7648ced4929d2bf78599585f51653", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE13507 licence not read", "asset:data:geo:GSE13507 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["with age, stage, and tumor microenvironment. In vivo, the expression of prognostic genes was iden"], "order_basis": "paper_text_order:1846", "id": "assay:1"}, {"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": ["Through the Univariate Cox regression algorithm, three genes of 119 ADFRMs were identified as independent factors to predict prognosis which were further utilized to establish the ADFRMs signature in BLCA."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}