Identification of hexosamine biosynthesis pathway as a novel prognostic signature and its correlation with immune infiltration in bladder cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36158580", "kind": "science-record", "revision": 4, "content_hash": "sha256:e5907fe449b65eb3629e67658d492d7b05f7763041f449d06fb26b6906777096", "created_at": "2026-11-01T18:15:26Z", "updated_at": "2026-11-01T22:50:10Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of hexosamine biosynthesis pathway as a novel prognostic signature and its correlation with immune infiltration in bladder cancer.", "doi": "10.3389/fmolb.2022.1009168", "pmid": "36158580", "authors": ["Yangyan Cui", "Hanyi Feng", "Jiakuan Liu", "Jiajun Wu", "Rujian Zhu", "Ruimin Huang", "Jun Yan"], "journal": "Frontiers in molecular biosciences", "year": 2022, "abstract": "Background: Urinary bladder cancer (UBC) is one of the common urological malignancies, lacking reliable biomarkers to predict clinical outcomes in UBC patients. Thus, it is needed to identify the novel diagnostic/prognostic biomarkers to stratify the high-risk UBC patients. As a shunt pathway of glycolysis, the hexosamine biosynthesis pathway (HBP) has been implicated in carcinogenesis. However, its prognostic value in UBC remains unclear. Methods: The RNA sequencing and mRNA microarray datasets were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus databases. The expression levels of five HBP genes were analyzed in normal and UBC samples, and their associations with stage, grade and survival were plotted. The performance of HBP risk group was evaluated by receiver-operating characteristics (ROC) curve. The HBP signature was generated by Gene Set Variation Analysis (GSVA) and its association with clinicopathological parameters and survival were analyzed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out to examine the potential biological functions of HBP using DAVID online tool. The infiltration estimation fraction of immune cells was performed using CIBERSORT-ABS algorithm. Gene set enrichment analysis (GSEA) was used to explore the potential function of HBP in tumor immunoregulation. Results: Four HBP genes were upregulated in UBCs compared to normal tissues in TCGA-BLCA dataset. The upregulation of all five HBP genes was significantly associated with tumor grade and stage of UBC in three independent UBC datasets. The expression of HBP genes predicted poor clinical outcomes in UBC patients in both TCGA-BLCA and GSE13507 datasets. The high-risk group based on HBP genes showed a poor prognosis. Furthermore, HBP signature was positively associated with tumor grade and stage in TCGA-BLCA dataset and with tumor grade, stage, distal metastasis and poor survival in GSE13507 dataset. Interestingly, high-HBP signature group exhibited a high infiltration of immune cells, particularly the macrophage population. Conclusion: We identified that HBP was a promising prognostic biomarker in UBC patients and strongly associated with immune infiltration.", "claims": [{"id": "claim-method", "statement": "The differences in overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS) between the high-risk and low-risk groups were estimated using the Kaplan-Meier method. Survival probability was calculated using Log-rank test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36158580", "locator": "sections[4] \"Survival analysis\" paragraph 2", "quote": "The differences in overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS) between the high-risk and low-risk groups were estimated using the Kaplan-Meier method. Survival probability was calculated using Log-rank test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36158580", "locator": "sections[18] \"Data availability statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "We identified that HBP was a promising prognostic biomarker in UBC patients and strongly associated with immune infiltration.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36158580", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "We identified that HBP was a promising prognostic biomarker in UBC patients and strongly associated with immune infiltration."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "We identified that HBP was a promising prognostic biomarker in UBC patients and strongly associated with immune infiltration.", "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:36158580"], "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:36158580", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fmolb.2022.1009168", "sha256": "sha256:1b1fd8a375bdea46ca41d8c499d0a29c7aa9be675253f14cefdbc2b2184dec02", "bytes": 45949, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fmolb.2022.1009168", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9493074", "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 datasets presented in this study can be found in online repositories. 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["survival_km"], "assets": ["source:pmid:36158580", "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": "2026-11-01T18:06:55Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 13802, "completion_tokens": 1821, "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:36158580", "type": "paper", "label": "pmid:36158580"}, {"id": "source:pmid:36158580", "type": "manuscript", "label": "PMID 36158580 full text"}, {"id": "data:geo:GSE13507", "type": "dataset", "label": "GEO GSE13507"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36158580", "type": "paper", "label": "pmid:36158580"}, {"id": "source:pmid:36158580", "type": "manuscript", "label": "PMID 36158580 full text"}, {"id": "data:geo:GSE13507", "type": "dataset", "label": "GEO GSE13507"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36158580", "type": "extraction", "used": ["source:pmid:36158580"], "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:36158580", "parent_hash": "sha256:16de4c86b747d560e634c0104953a8e170c16cae5edc699807f43f230e99d4f7", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE13507 licence not read", "asset:data:geo:GSE13507 not downloaded", "asset:data:geo:GSE3167 licence not read", "asset:data:geo:GSE3167 not downloaded", "asset:data:geo:GSE32894 licence not read", "asset:data:geo:GSE32894 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["c value in UBC remains unclear. Methods: The RNA sequencing and mRNA microarray datasets were downloaded"], "order_basis": "paper_text_order:558", "id": "assay:1"}, {"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": ["nclear. Methods: The RNA sequencing and mRNA microarray datasets were downloaded from The Cancer Gen"], "order_basis": "paper_text_order:582", "id": "assay:2"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["survival_km"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The differences in overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS) between the high-risk and low-risk groups were estimated using the Kaplan-Meier method. Survival probability was calculated using Log-rank test."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}