HES4 is a potential biomarker for bladder cancer: a Mendelian randomization study.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38370367", "kind": "science-record", "revision": 2, "content_hash": "sha256:e33a41e28e667817091355e505c1f45fea8e6c01bead0655ddbecab886f49cf5", "created_at": "2026-11-01T19:20:18Z", "updated_at": "2026-11-01T21:32:32Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "HES4 is a potential biomarker for bladder cancer: a Mendelian randomization study.", "doi": "10.7150/jca.92657", "pmid": "38370367", "authors": ["Zhiyong Tan", "Xiaorong Chen", "Haihao Li", "Yinglong Huang", "Shi Fu", "Mingxia Ding", "Jiansong Wang", "Haifeng Wang"], "journal": "Journal of Cancer", "year": 2024, "abstract": "Background: Patients with bladder cancer (BLCA) have a poor prognosis and little progress has been made in treatment. Therefore, the purpose of this work was to employ Mendelian randomization (MR) and transcriptome analysis to identify a novel biomarker that could be used to reliably diagnose BLCA. Methods: TCGA-BLCA and GSE121711 datasets were obtained from public databases. Genome-wide association study (GWAS) data of BLCA outcome (373,295 samples containing 9,904,926 single nucleotide polymorphisms) were obtained through the IEU OpenGWAS database. Differentially expressed genes were applied as exposure factors, and MR analysis was performed to identify genes that had a causal relationship with BLCA. Then, the patients were divided into high and low expression groups according to the expression levels of candidate genes, and genes with survival differences were identified. Univariate and multivariate Cox regression were used to investigate the prognostic value of the expression of these genes. A nomogram was constructed based on independent prognostic factors, and we analyzed the functions and pathways associated with the identified genes as well as their relationship with the immune microenvironment. Results: HES4 was identified as a biomarker. HES4 status, age, and stage were identified as independent prognostic factors, and an excellent nomogram was established. Bioinformatic analysis suggested that HES4 might be associated with the activation of the immune response, bone development, and cancer pathways. The BLCA samples were divided into high and low HES4 groups. The stromal score and 33 immune cells were remarkably different between the two groups, with HES4 expression being negatively correlated with macrophages and mast cells, and positively correlated with eosinophils and central memory CD4+ T cells. Finally, HES4 was up-regulated in cancer samples in both TCGA-BLCA and GSE121711 datasets. Conclusion: This study identified HES4 as an independent prognostic factor for BLCA outcome based on MR and transcriptome analysis, which provides useful information for future research on and treatment of BLCA.", "claims": [{"id": "claim-method", "statement": "The IVW method was used as the main MR analysis to identify genes that had a causal relationship with BLCA.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38370367", "locator": "sections[6] \"2.4 MR analysis\" paragraph 2", "quote": "The IVW method was used as the main MR analysis to identify genes that had a causal relationship with BLCA."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data availability statement1. The TCGA data are openly available at https://portal.gdc.cancer.gov/.2. The GEO data are openly available at https://www.ncbi.nlm.nih.gov/geo/.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38370367", "locator": "sections[32] \"ack\" paragraph 1", "quote": "Data availability statement1. The TCGA data are openly available at https://portal.gdc.cancer.gov/.2. The GEO data are openly available at https://www.ncbi.nlm.nih.gov/geo/."}], "state": "complete"}, {"id": "claim-target-result", "statement": "HES4 was identified as a biomarker.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38370367", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "HES4 was identified as a biomarker."}, {"asset": "source:pmid:38370367", "locator": "sections[20] \"3.3 Identification of genes with a causal relationship with BLCA\" paragraph 2", "quote": "These were NSUN5P2 (P = 0.025), GHRLOS (P = 0.000), TPM3P9 (P = 0.021), HES4 (P = 0.021), BATF2 (P = 0.002), PLXNA4 (P = 0.019), TGFBI (P = 0.014) and EPHB1 (P = 0.040)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "HES4 was identified as a biomarker.", "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:38370367"], "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": "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": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38370367", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7150/jca.92657", "sha256": "sha256:bae8234cd6dec397eb3671fd49c020f9c02b212b92e824769697704259181d8f", "bytes": 33787, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.7150/jca.92657", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10869984", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}], "gaps": []}, "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": 0.7, "band": "medium", "quote": "Cox regression"}}, {"id": "method-2", "family": "genetic_association", "specific": "gwas", "label": "Genetic association (GWAS / linkage / MR)", "dsl_operations": ["gwas_locus_scan"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["genotype_phenotype_table"], "evidence": {"score": 0.7, "band": "medium", "quote": "Genome-wide association study"}}, {"id": "method-3", "family": "genetic_association", "specific": "mendelian_randomisation", "label": "Genetic association (GWAS / linkage / MR)", "dsl_operations": ["mr_estimate"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["genotype_phenotype_table"], "evidence": {"score": 0.7, "band": "medium", "quote": "Mendelian randomization"}}, {"id": "method-4", "family": null, "specific": null, "label": "IVW", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The IVW method was used as the main MR analysis to identify genes that had a causal relationship with BLCA."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": 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": "R4", "reachable": false, "accessions": ["GSE121711 (GPL17586)"], "resolved_accessions": [], "statements": ["Data availability statement1. The TCGA data are openly available at https://portal.gdc.cancer.gov/.2. The GEO data are openly available at https://www.ncbi.nlm.nih.gov/geo/."], "basis": "The paper names GSE121711 (GPL17586), 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": ["cox_ph"], "assets": ["source:pmid:38370367"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "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": "2026-11-01T19:09:14Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 10319, "completion_tokens": 2461, "cached_tokens": 256}}, "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:38370367", "type": "paper", "label": "pmid:38370367"}, {"id": "source:pmid:38370367", "type": "manuscript", "label": "PMID 38370367 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38370367", "type": "paper", "label": "pmid:38370367"}, {"id": "source:pmid:38370367", "type": "manuscript", "label": "PMID 38370367 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38370367", "type": "extraction", "used": ["source:pmid:38370367"], "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:38370367", "parent_hash": "sha256:6dd37ab7e84dc144c5c231a874df2c296a5a7e9ba1764b4fa89facb1301f7ee8", "fork_of": null, "generation": 1}, "gaps": ["execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent"], "assays": [{"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": 0.7, "evidence": ["Cox regression"], "order_basis": "analysis_only", "id": "assay:1"}]}