Identification of hub genes associated with bladder cancer using bioinformatic analyses.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35706790", "kind": "science-record", "revision": 5, "content_hash": "sha256:3700ce3a983f13775dfbcac5d7d5fe3122e5d699256858c903b9bf22f93454d8", "created_at": "2026-11-01T18:14:40Z", "updated_at": "2026-11-01T22:49:18Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of hub genes associated with bladder cancer using bioinformatic analyses.", "doi": "10.21037/tcr-22-1004", "pmid": "35706790", "authors": ["Wei Zheng", "Yubo Zhao", "Tengshuang Wang", "Xiaoling Zhao", "Zhangsen Tan"], "journal": "Translational cancer research", "year": 2022, "abstract": "Background: Bladder cancer (BLCA) is the ninth most common cancer worldwide, with high mortality and recurrence rates. Studies have increasingly reported that molecular diagnosis contributes to the early diagnosis and prognostic assessment of diseases. Thus, this study aims to find new biomarkers for the diagnosis and prognosis of BLCA.\nMethods: The microarray datasets GSE147983 and The Cancer Genome Atlas (TCGA)-BLCA mRNA were obtained from the Gene Expression Omnibus (GEO) and TCGA. Differentially expressed genes (DEGs) were screened using the R \"Limma\" package. The \"ClusterProfiler\" package was used to conduct Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the DEGs. A DEG protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized using Cytoscape. The functional module was reanalyzed using Cytoscape's Molecular Complex Detection (\"MCODE\") plugin, and key genes related to BLCA were identified via the \"cytoHubba\" plugin. Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and the Tumor Immune Estimation Resource (TIMER) were used to verify the correlation between hub gene expression and immunity. A survival analysis of hub genes was performed using the Kaplan-Meier Plotter online tool.\nResults: A total of 355 DEGs were screened out, including 236 upregulated and 119 downregulated DEGs. Some of the GO terms and pathways, such as chromosome separation, cell cycle, and cell senescence, were found to be significantly enriched in the DEGs. The key genes were kinesin family member 11 (KIF11), DLG associated protein 5 (DLGAP5), non-SMC condensin I complex subunit G (NCAPG), cell division cycle 20 (CDC20), cyclin B2 (CCNB2), BUB1 mitotic checkpoint serine (BUB1B), TPX2 microtubule nucleation factor (TPX2), NUF2 component of NDC80 kinetochore complex (NUF2), kinesin family member 2C (KIF2C), and cyclin B1 (CCNB1). Nine of them were immune-related, including KIF11, DLGAP5, NCAPG, CDC20, CCNB2, BUB1B, NUF2, KIF2C, and CCNB1. Survival analysis showed that the overexpression of BUB1B, CCNB1, CDC20, and DLGAP5 significantly reduced overall survival (OS) in patients with BLCA.\nConclusions: This study provided a theoretical basis for elucidating the pathogenesis and evaluating the prognosis of BLCA by screening potential biomarkers of BLCA.", "claims": [{"id": "claim-method", "statement": "The TCGA-BLCA mRNA dataset was processed using the “Limma” package in R version 4.0.4 (64 bit; The R Foundation for Statistical Computing, Vienna, Austria) (14).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35706790", "locator": "sections[4] \"Data processing\" paragraph 2", "quote": "The TCGA-BLCA mRNA dataset was processed using the “Limma” package in R version 4.0.4 (64 bit; The R Foundation for Statistical Computing, Vienna, Austria) (14)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The GSE147983 [GPL20301, Illumina HiSeq 4000 (Homo sapiens)] dataset containing 4 control and 4 BLCA tissue samples was obtained from the GEO database (https://www.ncbi.nlm.nih.gov/geo/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35706790", "locator": "sections[3] \"Microarray data\" paragraph 3", "quote": "The GSE147983 [GPL20301, Illumina HiSeq 4000 (Homo sapiens)] dataset containing 4 control and 4 BLCA tissue samples was obtained from the GEO database (https://www.ncbi.nlm.nih.gov/geo/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Overexpression of BUB1B, CCNB1, CDC20, and DLGAP5 was associated with significantly reduced overall survival in patients with bladder cancer.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35706790", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Survival analysis showed that the overexpression of BUB1B, CCNB1, CDC20, and DLGAP5 significantly reduced overall survival (OS) in patients with BLCA."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Overexpression of BUB1B, CCNB1, CDC20, and DLGAP5 was associated with significantly reduced overall survival in patients with bladder cancer.", "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:35706790"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": [], "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:group_comparison_wilcoxon", "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon", "step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35706790", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21037/tcr-22-1004", "sha256": "sha256:67d1aae9d9e5ddc8d33f9527c2092a1ccd2cfdccfcf629fd40d6d38c9933a15d", "bytes": 36851, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.21037/tcr-22-1004", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9189183", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}], "gaps": []}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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": 1.0, "band": "verbatim", "quote": "The TCGA-BLCA mRNA dataset was processed using the “Limma” package in R version 4.0.4 (64 bit; The R Foundation for Statistical Computing, Vienna, Austria) (14)."}}, {"id": "method-2", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.7, "band": "medium", "quote": "Kaplan-Meier"}}, {"id": "method-3", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 0.7, "band": "medium", "quote": "Limma"}}, {"id": "method-4", "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"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor", "method.group_comparison_wilcoxon"]}, "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": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R1", "expressible": false, "required_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: wilcoxon."}, "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": "R4", "reachable": false, "accessions": ["GSE147983 [GPL20301"], "resolved_accessions": [], "statements": ["The GSE147983 [GPL20301, Illumina HiSeq 4000 (Homo sapiens)] dataset containing 4 control and 4 BLCA tissue samples was obtained from the GEO database (https://www.ncbi.nlm.nih.gov/geo/)."], "basis": "The paper names GSE147983 [GPL20301, but the accession does not resolve in the repository (no reason recorded), so the data cannot be reached from here. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:35706790"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "group_comparison_wilcoxon", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:None"]}, "gaps": ["data:accession_absent"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:50:30Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 5, "usage": {"prompt_tokens": 12167, "completion_tokens": 3066, "cached_tokens": 128}}, "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:35706790", "type": "paper", "label": "pmid:35706790"}, {"id": "source:pmid:35706790", "type": "manuscript", "label": "PMID 35706790 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35706790", "type": "paper", "label": "pmid:35706790"}, {"id": "source:pmid:35706790", "type": "manuscript", "label": "PMID 35706790 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35706790", "type": "extraction", "used": ["source:pmid:35706790"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-None", "type": "accession_resolution", "used": ["data:geo:None"], "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:35706790", "parent_hash": "sha256:a20bb25c3e326600116641b29577828149485655cc9eca8e1908305bf342896f", "fork_of": null, "generation": 4}, "gaps": ["execution.not_run", "method.group_comparison_wilcoxon", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent", "step:run_analysis blocked on method:group_comparison_wilcoxon"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["iagnosis and prognosis of BLCA. 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