A novel immune-related gene pair prognostic signature for predicting overall survival in bladder cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34266411", "kind": "science-record", "revision": 6, "content_hash": "sha256:9f3d85b96e77f2901451489bc0c3bfe64dbc718818e3b1d4e4ba481c0c4fd01d", "created_at": "2026-11-01T15:41:43Z", "updated_at": "2026-11-01T21:25:47Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A novel immune-related gene pair prognostic signature for predicting overall survival in bladder cancer.", "doi": "10.1186/s12885-021-08486-0", "pmid": "34266411", "authors": ["Yang Fu", "Shanshan Sun", "Jianbin Bi", "Chuize Kong", "Lei Yin"], "journal": "BMC cancer", "year": 2021, "abstract": "BACKGROUND: Bladder cancer (BC) is the ninth most common malignant tumor. We constructed a risk signature using immune-related gene pairs (IRGPs) to predict the prognosis of BC patients.\nMETHODS: The mRNA transcriptome, simple nucleotide variation and clinical data of BC patients were downloaded from The Cancer Genome Atlas (TCGA) database (TCGA-BLCA). The mRNA transcriptome and clinical data were also extracted from Gene Expression Omnibus (GEO) datasets (GSE31684). A risk signature was built based on the IRGPs. The ability of the signature to predict prognosis was analyzed with survival curves and Cox regression. The relationships between immunological parameters [immune cell infiltration, immune checkpoints, tumor microenvironment (TME) and tumor mutation burden (TMB)] and the risk score were investigated. Finally, gene set enrichment analysis (GSEA) was used to explore molecular mechanisms underlying the risk score.\nRESULTS: The risk signature utilized 30 selected IRGPs. The prognosis of the high-risk group was significantly worse than that of the low-risk group. We used the GSE31684 dataset to validate the signature. Close relationships were found between the risk score and immunological parameters. Finally, GSEA showed that gene sets related to the extracellular matrix (ECM), stromal cells and epithelial-mesenchymal transition (EMT) were enriched in the high-risk group. In the low-risk group, we found a number of immune-related pathways in the enriched pathways and biofunctions.\nCONCLUSIONS: We used a new tool, IRGPs, to build a risk signature to predict the prognosis of BC. By evaluating immune parameters and molecular mechanisms, we gained a better understanding of the mechanisms underlying the risk signature. This signature can also be used as a tool to predict the effect of immunotherapy in patients with BC.", "claims": [{"id": "claim-method", "statement": "Pearson test was used for all correlation analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34266411", "locator": "sections[8] \"Statistical analysis\" paragraph 2", "quote": "Pearson test was used for all correlation analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated and/or analyzed during the current study are available in the TCGA repository (https://portal.gdc.cancer.gov/), GSE31684 repository, (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE31684), and IMvigor210 (http://research-pub.gene.com/IMvigor210CoreBiologies/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34266411", "locator": "sections[21] \"Availability of data and materials\" paragraph 2", "quote": "The datasets generated and/or analyzed during the current study are available in the TCGA repository (https://portal.gdc.cancer.gov/), GSE31684 repository, (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE31684), and IMvigor210 (http://research-pub.gene.com/IMvigor210CoreBiologies/)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "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:34266411"], "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:GSE31684"], "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:GSE31684"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34266411", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12885-021-08486-0", "sha256": 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"title": "Combination of a novel gene expression signature with a clinical nomogram improves the prediction of survival in high-risk 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": "asset:table:pmid:34266411:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b34723120da6f770917b5500eba9373e3f820cf349fc597b14e9529f66db30c4", "bytes": 824, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[1]#Tab1", "version": null, "note": "Characteristics of the patients obtained from the TCGA database and GSE31684", "structure": {"pmcid": "PMC8281685", "section_index": 3, "section_title": "Data acquisition", "row_count": 22, "column_count": 4}, "table": {"label": "Table 1", "caption": "Characteristics 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motif chemokine ligand 13", "0.025"], ["ERAP2", "endoplasmic reticulum aminopeptidase 2", "FAM3B", "FAM3 metabolism regulating signaling molecule B", "0.390"], ["CXCL9", "C-X-C motif chemokine ligand 9", "PTN", "pleiotrophin", "−0.182"], ["CXCL11", "C-X-C motif chemokine ligand 11", "MMP9", "matrix metallopeptidase 9", "−0.334"], ["CXCL6", "C-X-C motif chemokine ligand 6", "DES", "desmin", "−0.055"], ["CXCL12", "C-X-C motif chemokine ligand 12", "IL18", "interleukin 18", "0.210"], ["CXCL12", "C-X-C motif chemokine ligand 12", "C5AR1", "complement C5a receptor 1", "0.128"], ["CXCL13", "C-X-C motif chemokine ligand 13", "DEFB1", "defensin beta 1", "−0.010"], ["CXCL13", "C-X-C motif chemokine ligand 13", "CCL11", "C-C motif chemokine ligand 11", "−0.087"], ["CXCL13", "C-X-C motif chemokine ligand 13", "GREM1", "gremlin 1, DAN family BMP antagonist", "−0.112"], ["CXCL13", "C-X-C motif chemokine ligand 13", "PTN", "pleiotrophin", "−0.254"], ["DEFB1", "defensin beta 1", "TNFSF13B", "TNF 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risk in TCGA", "structure": {"pmcid": "PMC8281685", "section_index": 10, "section_title": "Construction of the IRGP signature", "row_count": 19, "column_count": 5}, "table": {"label": "Table 4", "caption": "Differences in the characteristics of BC patients between the high risk and low risk in TCGA", "rows": [["Basic information", "", "Low risk", "High risk", "P value"], ["Age", "", "", "", "0.021"], ["", "≤ 69", "138", "75", ""], ["", "> 69", "100", "87", ""], ["Gender", "", "", "", "0.143"], ["", "Female", "55", "48", ""], ["", "Male", "183", "114", ""], ["Stage", "", "", "", "< 0.001"], ["", "I&II", "93", "36", ""], ["", "III&IV", "143", "126", ""], ["T", "", "", "", "0.007"], ["", "T1&T2", "83", "38", ""], ["", "T3&T4", "133", "114", ""], ["N", "", "", "", "0.002"], ["", "N0", "152", "81", ""], ["", "N1–3", "61", "65", ""], ["M", "", "", "", "< 0.001"], ["", "M0", "132", "61", ""], ["", "M1", "2", "9", ""]], "row_count": 19, "column_count": 5, "numeric_cells": 33, "header_rows": 1, 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["GO_COLLAGEN_CONTAINING_EXTRACELLULAR_MATRIX", "2.389", "< 0.001", "< 0.001"], ["GO_EXTRACELLULAR_STRUCTURE_ORGANIZATION", "2.301", "< 0.001", "0.001"], ["GO_EXTRACELLULAR_MATRIX_COMPONENT", "2.264", "< 0.001", "0.002"], ["GO_COLLAGEN_FIBRIL_ORGANIZATION", "2.253", "< 0.001", "0.002"], ["GO_COLLAGEN_BINDING", "2.250", "< 0.001", "0.002"], ["GO_COLLAGEN_TRIMER", "2.241", "0.002", "0.003"], ["GO_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT_CONFERRING_TENSILE_STRENGTH", "2.222", "< 0.001", "0.003"], ["GO_POSITIVE_REGULATION_OF_EPITHELIAL_TO_MESENCHYMAL_TRANSITION", "2.219", "< 0.001", "0.003"], ["GO_REGULATION_OF_CHONDROCYTE_DIFFERENTIATION", "2.175", "< 0.001", "0.005"], ["GO_EXTRACELLULAR_MATRIX_BINDING", "2.105", "< 0.001", "0.011"], ["GO_POSITIVE_REGULATION_OF_FIBROBLAST_PROLIFERATION", "2.042", "< 0.001", "0.018"], ["GO_ENDOTHELIAL_CELL_PROLIFERATION", "1.990", "0.002", "0.024"], ["GO_POSITIVE_REGULATION_OF_ENDOTHELIAL_CELL_PROLIFERATION", "1.942", "0.002", "0.031"], 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"access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[4]#Tab8", "version": null, "note": "Gene sets enriched in low risk phenotype via KEGG", "structure": {"pmcid": "PMC8281685", "section_index": 12, "section_title": "GSEA", "row_count": 14, "column_count": 4}, "table": {"label": "Table 8", "caption": "Gene sets enriched in low risk phenotype via KEGG", "rows": [["Gene set name", "NES", "NOM p-val", "FDR q-val"], ["KEGG_PEROXISOME", "−1.986", "< 0.001", "1.467"], ["KEGG_LINOLEIC_ACID_METABOLISM", "−1.934", "< 0.001", "1.397"], ["KEGG_ANTIGEN_PROCESSING_AND_PRESENTATION", "−2.150", "0.002", "1.568"], ["KEGG_CYTOSOLIC_DNA_SENSING_PATHWAY", "−2.070", "0.004", "1.419"], ["KEGG_RIG_I_LIKE_RECEPTOR_SIGNALING_PATHWAY", "−1.912", "0.008", "1.425"], ["KEGG_AUTOIMMUNE_THYROID_DISEASE", "−2.013", "0.008", "1.479"], ["KEGG_GRAFT_VERSUS_HOST_DISEASE", "−1.959", "0.008", "1.425"], ["KEGG_ALLOGRAFT_REJECTION", "−1.926", 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