Identification of grade-related genes and construction of a robust genomic-clinicopathologic nomogram for predicting recurrence of bladder cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33217824", "kind": "science-record", "revision": 7, "content_hash": "sha256:9e843815a8fdb9a3331f08dfc85242a768957be3d8cbe04eb601610706428e4a", "created_at": "2026-11-01T15:41:16Z", "updated_at": "2026-11-01T22:02:34Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of grade-related genes and construction of a robust genomic-clinicopathologic nomogram for predicting recurrence of bladder cancer.", "doi": "10.1097/MD.0000000000023179", "pmid": "33217824", "authors": ["Xiqi Peng", "Jingyao Wang", "Dongna Li", "Xuan Chen", "Kaihao Liu", "Chunduo Zhang", "Yongqing Lai"], "journal": "Medicine", "year": 2020, "abstract": "BACKGROUND: Bladder cancer (BC) is a common tumor in the urinary system with a high recurrence rate. The individualized treatment and follow-up after surgery is the key to a successful outcome. Currently, the surveillance strategies are mainly depending on tumor stage and grade. Previous evidence has proved that tumor grade was a significant and independent risk factor of BC recurrence. Exploring the grade-related genes may provide us a new approach to predict prognosis and guide the post-operative treatment in BC patients.\nMETHODS: In this study, the weighted gene co-expression network analysis was applied to identify the hub gene module correlated with BC grade using GSE71576. After constructing a protein-protein interaction (PPI) network with the hub genes inside the hub gene module, we identified some potential core genes. TCGA and another independent dataset were used for further validation.\nRESULTS: The results revealed that the expression of AURKA, CCNA2, CCNB1, KIF11, TTK, BUB1B, BUB1, and CDK1 were significantly higher in high-grade BC, showing a strong ability to distinguish BC grade. The expression levels of the 8 genes in normal, paracancerous, tumorous, and recurrent bladder tissues were progressively increased. By conducting survival analysis, we proved their prognostic value in predicting the recurrence of BC. Eventually, we constructed a prognostic nomogram by combining the 8-core-gene panel with clinicopathologic features, which had shown great performance in predicting the recurrence of BC.\nCONCLUSION: We identified 8 core genes that revealed a significant correlation with the tumor grade as well as the recurrence of BC. Finally, we proved the value of a novel prognostic nomogram for predicting the relapse-free survival of BC patients after surgery, which could guide their treatment and follow-up.", "claims": [{"id": "claim-data-access", "statement": "The datasets generated during and/or analyzed during the current study are publicly available.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33217824", "locator": "sections[28] \"fn-group\" paragraph 1", "quote": "The datasets generated during and/or analyzed during the current study are publicly available."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "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:33217824"], "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": "blocked", "blocked_on": "method:student_t", "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": ["step:run_analysis blocked on method:student_t"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33217824", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1097/MD.0000000000023179", "sha256": "sha256:df54763c00e3cb5b7656d89ba81fed69e2a1f6c2b1c071f955dbc7ce01c9c32a", "bytes": 34945, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1097/MD.0000000000023179", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7676566", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "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 datasets generated during and/or analyzed during the current study are publicly available.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets generated during and/or analyzed during the current study are publicly available.", "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}}, {"id": "data:geo:GSE71576", "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=GSE71576", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE71576", "version": null, "note": "The datasets generated during and/or analyzed during the current study are publicly available.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets generated during and/or analyzed during the current study are publicly available.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1838823", "GSM1838824", "GSM1838825", "GSM1838826", "GSM1838827", "GSM1838828", "GSM1838829", "GSM1838830", "GSM1838831", "GSM1838832", "GSM1838833", "GSM1838834", "GSM1838835", "GSM1838836", "GSM1838837", "GSM1838838", "GSM1838839", "GSM1838840", "GSM1838841", "GSM1838842", "GSM1838843", "GSM1838844", "GSM1838845", "GSM1838846", "GSM1838847", "GSM1838848", "GSM1838849", "GSM1838850", "GSM1838851", "GSM1838852", "GSM1838853", "GSM1838854", "GSM1838855", "GSM1838856", "GSM1838857", "GSM1838858", "GSM1838859", "GSM1838860", "GSM1838861", "GSM1838862", "GSM1838863", "GSM1838864", "GSM1838865", "GSM1838866"], "sample_count": 44, "group_sizes": null, "group_sizes_basis": null, "platform": "6244", "taxon": "Homo sapiens", "title": "Integration analysis of three omics data using penalized regression methods: An application to bladder cancer (expression)", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:33217824:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:0c884f4ea4b3c13bfa0a1515537ad14861938b858488327d613e0a1c43deb007", "bytes": 818, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[19]/table-wrap[1]#T1", "version": null, "note": "The association between the 8-core-gene panel and clinicopathologic features with RFS of BC patients.", "structure": {"pmcid": "PMC7676566", "section_index": 19, "section_title": "Nomogram construction and assessment", "row_count": 8, "column_count": 5}, "table": {"label": "Table 1", "caption": "The association between the 8-core-gene panel and clinicopathologic features with RFS of BC patients.", "rows": [["", "Univariate analysis", "Multivariate analysis"], ["Variable", "HR (95% CI)", "P value", "HR (95% CI)", "P value"], ["Gender (male vs female)", "1.164 (0.805–1.681)", ".42", "", ""], ["Age", "1.005 (0.989–1.022)", ".511", "", ""], ["Smoking (yes vs no)", "1.202 (0.858–1.682)", ".285", "1.230 (0.878–1.723)", ".229"], ["Tumor grade (high vs low)", "2.917 (0.72–11.82)", ".134", "1.304 (0.3122–5.444)", ".716"], ["Tumor stage", "1.704 (1.374–2.113)", "<.001", "1.671 (1.343–2.080)", "<.001"], ["Gene panel risk score", "2.735 (1.703–4.165)", "<.001", "2.537 (1.587–4.056)", "<.001"]], "row_count": 8, "column_count": 5, "numeric_cells": 22, "header_rows": 2, "locator": "section[19]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:33217824:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:4ab3bbbd4d979bf672149b58088ba90aac9161a670c94c14c9a804dd17e8d60e", "bytes": 448, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[19]/table-wrap[2]#T2", "version": null, "note": "Harrell concordance indexes of the 8-core-gene panel, clinicopathologic features∗, and nomogram in different cohorts.", "structure": {"pmcid": "PMC7676566", "section_index": 19, "section_title": "Nomogram construction and assessment", "row_count": 4, "column_count": 4}, "table": {"label": "Table 2", "caption": "Harrell concordance indexes of the 8-core-gene panel, clinicopathologic features∗, and nomogram in different cohorts.", "rows": [["Cohort", "8-core-gene panel", "Clinicopathologic features", "Nomogram"], ["Training", "0.651", "0.661", "0.708"], ["Validation", "0.610", "0.603", "0.659"], ["Entire", "0.59", "0.635", "0.667"]], "row_count": 4, "column_count": 4, "numeric_cells": 10, "header_rows": 1, "locator": "section[19]/table-wrap[2]#T2"}}], "gaps": ["asset:data:geo:GSE13507 not downloaded", "asset:data:geo:GSE13507 licence not read", "asset:data:geo:GSE71576 not downloaded", "asset:data:geo:GSE71576 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Student t test"}}, {"id": "method-2", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "ANOVA"}}, {"id": "method-3", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "log-rank"}}, {"id": "method-4", "family": "correlation_analysis", "specific": "spearman", "label": "Correlation analysis", "dsl_operations": ["spearman_rho"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Spearman correlation"}}, {"id": "method-5", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "protein-protein interaction"}}, {"id": "method-6", "family": null, "specific": null, "label": "Weighted gene co-expression network analysis (WGCNA) using GSE71576 data acquired from the Gene Expression Omnibus (GEO) database", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "reordered", "quote": "“Using the “WGCNA” package in R,[12] we created a scale-free co-expression network of the filtered genes.” “Normalized data from dataset GSE71576 were acquired from the GEO database.”"}}], "targets": [], "gaps": ["method.reader_named_unmapped", "method.student_t"]}, "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": false, "required_operations": [], "missing_operations": ["student_t"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: student_t_test."}, "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": ["GSE71576", "GSE13507"], "resolved_accessions": ["GSE71576", "GSE13507"], "statements": ["The datasets generated during and/or analyzed during the current study are publicly available."], "basis": "The paper names GSE71576, GSE13507 in Gene Expression Omnibus (GEO) database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:33217824", "data:geo:GSE13507", "asset:table:pmid:33217824:1", "asset:table:pmid:33217824:2"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "student_t", "unlocks_papers": null, "priority": null}], "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": "2026-10-31T18:24:24Z", "independence": "single_reader"}, "evidence_check": {"method": "reordered", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 26086, "completion_tokens": 1877, "cached_tokens": 784}}, "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:33217824", "type": "paper", "label": "pmid:33217824"}, {"id": "source:pmid:33217824", "type": "manuscript", "label": "PMID 33217824 full text"}, {"id": "data:geo:GSE13507", "type": "dataset", "label": "GEO GSE13507"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33217824", "type": "paper", "label": "pmid:33217824"}, {"id": "source:pmid:33217824", "type": "manuscript", "label": "PMID 33217824 full text"}, {"id": "data:geo:GSE13507", "type": "dataset", "label": "GEO GSE13507"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33217824", "type": "extraction", "used": ["source:pmid:33217824"], "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:33217824", "parent_hash": "sha256:21c3add451ffc80497c6204e99bd5c56a8f829d25c4748c958bb0e8896ddf8ec", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE13507 licence not read", "asset:data:geo:GSE13507 not downloaded", "asset:data:geo:GSE71576 licence not read", "asset:data:geo:GSE71576 not downloaded", "execution.not_run", "method.reader_named_unmapped", "method.student_t", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:student_t"], "assays": [{"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Student t test"], "order_basis": "analysis_only", "id": "assay:1"}]}