Identification of a novel signature based on unfolded protein response-related gene for predicting prognosis in bladder cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34930465", "kind": "science-record", "revision": 3, "content_hash": "sha256:fbdaa4e20c3c9be43121dd5d3b4b62d021f56341e6dc500076f32d96909c1c7e", "created_at": "2026-11-01T17:36:38Z", "updated_at": "2026-11-01T21:26:49Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of a novel signature based on unfolded protein response-related gene for predicting prognosis in bladder cancer.", "doi": "10.1186/s40246-021-00372-x", "pmid": "34930465", "authors": ["Ke Zhu", "Liu Xiaoqiang", "Wen Deng", "Gongxian Wang", "Bin Fu"], "journal": "Human genomics", "year": 2021, "abstract": "BACKGROUND: The unfolded protein response (UPR) served as a vital role in the progression of tumors, but the molecule mechanisms of UPR in bladder cancer (BLCA) have been not fully investigated.\nMETHODS: We identified differentially expressed unfolded protein response-related genes (UPRRGs) between BLCA samples and normal bladder samples in the Cancer Genome Atlas (TCGA) database. Univariate Cox analysis and the least absolute shrinkage and selection operator penalized Cox regression analysis were used to construct a prognostic signature in the TCGA set. We implemented the validation of the prognostic signature in GSE13507 from the Gene Expression Omnibus database. The ESTIMATE, CIBERSORT, and ssGSEA algorithms were used to explore the correlation between the prognostic signature and immune cells infiltration as well as key immune checkpoints (PD-1, PD-L1, CTLA-4, and HAVCR2). GDSC database analyses were conducted to investigate the chemotherapy sensitivity among different groups. GSEA analysis was used to explore the potential mechanisms of UPR-based signature.\nRESULTS: A prognostic signature comprising of seven genes (CALR, CRYAB, DNAJB4, KDELR3, CREB3L3, HSPB6, and FBXO6) was constructed to predict the outcome of BLCA. Based on the UPRRGs signature, the patients with BLCA could be classified into low-risk groups and high-risk groups. Patients with BLCA in the low-risk groups showed the more favorable outcomes than those in the high-risk groups, which was verified in GSE13507 set. This signature could serve as an autocephalous prognostic factor in BLCA. A nomogram based on risk score and clinical characteristics was established to predict the over survival of BLCA patients. Furthermore, the signature was closely related to immune checkpoints (PD-L1, CTLA-4, and HAVCR2) and immune cells infiltration including CD8+ T cells, follicular helper T cells, activated dendritic cells, and M2 macrophages. GSEA analysis indicated that immune and carcinogenic pathways were enriched in high-risk group.\nCONCLUSIONS: We identified a novel unfolded protein response-related gene signature which could predict the over survival, immune microenvironment, and chemotherapy response of patients with bladder cancer.", "claims": [{"id": "claim-method", "statement": "Univariate Cox analysis and the least absolute shrinkage and selection operator penalized Cox regression analysis were used to construct a prognostic signature in the TCGA set.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34930465", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Univariate Cox analysis and the least absolute shrinkage and selection operator penalized Cox regression analysis were used to construct a prognostic signature in the TCGA set."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw data of this study are derived from the TCGA database (https://portal.gdc.cancer.gov/) and GEO data portal (https://www.ncbi.nlm.nih.gov/geo/), which are publicly available databases.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34930465", "locator": "sections[31] \"Availability of data and materials\" paragraph 2", "quote": "The raw data of this study are derived from the TCGA database (https://portal.gdc.cancer.gov/) and GEO data portal (https://www.ncbi.nlm.nih.gov/geo/), which are publicly available databases."}], "state": "complete"}, {"id": "claim-target-result", "statement": "We identified a novel unfolded protein response-related gene signature which could predict the over survival, immune microenvironment, and chemotherapy response of patients with bladder cancer.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34930465", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "We identified a novel unfolded protein response-related gene signature which could predict the over survival, immune microenvironment, and chemotherapy response of patients with bladder cancer."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "We identified a novel unfolded protein response-related gene signature which could predict the over survival, immune microenvironment, and chemotherapy response of 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:34930465"], "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:34930465", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s40246-021-00372-x", "sha256": 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